فتحي الهادي عمر الصالح
عضو هيئة تدريس قار
المؤهل العلمي: دكتوراه
الدرجة العلمية: أستاذ
التخصص: كيمياء عضوية - كيمياء
قسم علوم الكيمياء - مدرسة العلوم الأساسية
Experimental design optimization of RP-HPLC method for simultaneous estimation of metsulfuron-methyl, chlorantraniliprole and chlorimuron-ethyl residues in stems of Oryza sativaJournal Article
The study aims to develop a chemometrics optimized D-optimal mixture design approach assisted RP- HPLC method for the determination of pesticide residues of metsulfuron-methyl, chlorantraniliprole, and chlorimu- ron-ethyl in the stems of Oryza sativa. Chromatographic separation was achieved on a C18 column using a mobile phase consisting of a pH 3.5 phosphate buffer and acetonitrile in the ratio 85:15.
Shanta Kumari Adiki, Prakash Katakam, Fathi H. Assaleh, (10-2021), Future Journal of Pharmaceutical Sciences: springer, 7 (217), 1-11
An Update on Therapeutic Repurposing Strategies for COVID-19Journal Article
The severe acute respiratory syndrome coronavirus 2, well known as COVID-19 has become the current health distress to the entire world. In the pandemic scenario the research on the rapid development of new drug molecules is highly risky and tedious process. The current COVID-19 emergency demands an urgent development of possible strategies to protect people at high risk of infection and hence the drug repurposing became an emerging approach to fight COVID-19. This review summarizes an update on various therapeutic strategies with special attention on repurposing of drugs to fight against SARS-CoV-2 worldwide. The investigation of existing drugs for new therapeutic purposes is one line of scientific research followed to develop safe and effective COVID-19 treatments. Broad-spectrum antiviral agents (BSAAs) that have been believed to be safe through testing on early phase clinical trials have been hyped as good drug repurposing candidates. Broad-spectrum antiviral drugs such as Ribavirin, Umifenovir were advised for COVID-19 treatment. Some antibiotics may be repurposed as COVID-19 treatments such as teicoplanin, oritavancin, dalbavancin, monensin and azithromycin. Ivermectin an antiparasitic is recently repurposed. Hydroxychloroquine and chloroquine, having immunomodulating effect on humans, have been shown to have antiviral activity at starting and post-entry stages of the SARS-CoV-2 infection. There is a need for global health emergency to call for a courageous, global response at the political and governmental levels. Therefore, the regulatory agencies must act swiftly to lessen any financial obstacles involving private companies and update guidelines for drug licenses by repurposing if necessary.
Prakash Katakam, Shanta K. Adiki, Fathi H. Assaleh, Mohammed M. Ahmed, (04-2020), Indo Global J. Pharm. Sci.: iGlobal Research & Publishing Foundation, 10 (1), 12-18
Conformational stability of 5-substituted orotic acid derivatives analysed by measuring 13C NMR chemical shifts and applying linear free energy relationshipsJournal Article
Conformational stability of various 5-substituted orotic acid derivatives was studied by applying linear free energy relationships (LFER) to the 13C NMR chemical shifts. The correlation analysis for the substituent-induced chemical shifts (SCS) with inductive (σI), and various resonance (σR) parameters were carried out through Single Substituent Parameter (SSP) and Dual Substituent Parameter (DSP) methods, and multiple regression analysis. Good Hammett correlations for all carbons were obtained, while electrophilic substituent constants better fitted for C2 carbon with electron-donor substituents. Conformational analysis of various derivatives using RB3LYP/6-311++G (3df,3dp) DFT method, together with 13C NMR data suggests that most of the substituted orotic acid derivatives exist in planar conformation, except nitro and alkyl substituted derivatives. Internal rotation of carboxylic group showed significant impact on the extent of conjugative interaction making syn conformation more stable in all the derivatives studied. Further, of all 5-substituted orotic acid derivatives, diketo form proved to be the most stable form compared to zwitterionic and enol tautomeric forms. Optimized geometries and transmission effects of particular substituent through well-defined π-resonance units suggest that these units behave as isolated as well as conjugated fragments, depending on the type of substituent
Fathi Assaleh, Aleksandar D. Marinković, Jasmina Nikolić, Nevena Ž.Prlainović, Saša Drmanić, Mohammad M.Khan, Bratislav Ž. Jovanović, (12-2019), Arabian Journal of Chemistry: Elsevier, 12 (8), 3357-3366
Solvatochromism and azo–hydrazo tautomerism of novel arylazo pyridone dyes: Experimental and quantum chemical studyJournal Article
The state of the tautomeric equilibria of eleven arylazo pyridone dyes was evaluated from UV–Vis absorption spectra with the aid of the quantum mechanical modeling. NMR analysis and theoretical calculations, by using PCM/ωB97X-D/6-311G(d,p) method, confirmed that prepared compounds exist mainly in Hydrazo form. Internal hydrogen bonding in Hydrazo tautomer, analyzed by AIM topological analysis and total electron density at the bond critical point (BCP), confirmed a presence of strong hydrogen bond which contributes to higher stability of Hydrazo form. Linear solvation energy relationships (LSERs) rationalized solvent influence on solvatochromism of all compounds in Hydrazoform and KT by using Kamlet–Taft model. Linear free energy relationships(LFERs) were applied to the substituent-induced NMR chemical shifts (SCS) using SSP (single substituent parameter) and DSP (dual substituent parameter) model. Density plots over the highest occupied (HOMO) and lowest unoccupied molecular orbitals (LUMO) energy surface provide information on the charge transfer during excitation. The molecular electrostatic potential (MEP) surface map was plotted over the optimized geometry of the molecules in order to visualize electron density distribution and explain origin of solvent/solute interactions.
Ismail Ajaj, Fathi Assaleh, Jasmina Markovski, Milica Rančić, Danijela Brkoviće, Miloš Milčić, Aleksandar D. Marinković, (12-2019), Arabian Journal of Chemistry: Elsevier, 12 (8), 3463-3478
Detailed solvent, structural, quantum chemical study and antimicrobial activity of isatin Schiff baseJournal Article
The ratios of E/Z isomers of sixteen synthesized 1,3-dihydro-3-(substituted phenylimino)-2H-indol-2-one were studied using experimental and theoretical methodology. Linear solvation energy relationships (LSER) rationalized solvent influence of the solvent–solute interactions on the UV–Vis absorption maximashifts (νmax) of both geometrical isomers using the Kamlet-Taft equation. Linear free energy relationships (LFER) in the form of single substituent parameter equation (SSP) was used to analyze substituent effect on pKa, NMR chemical shifts and νmax values. Electron charge density was obtained by the use of Quantum Theory of Atoms in Molecules, i.e. Bader's analysis. The substituent and solvent effect on intramolecular charge transfer (ICT) were interpreted with the aid of time-dependent density functional (TD-DFT) method. Additionally, the results of TD-DFT calculations quantified the efficiency of ICT from the calculated charge-transfer distance (DCT) and amount of transferred charge (QCT). The antimicrobial activity was evaluated using broth microdilution method. 3D QSAR modeling was used to demonstrate the influence of substituents effect as well as molecule geometry on antimicrobial activity
Dominik R. Brkić, Aleksandra R. Božić, Aleksandar D. Marinković, Miloš K. Milčić, Nevena Ž. Prlainović, Fathi .H .O Assaleh, Ilija N. Cvijetić, Jasmina B. Nikolić, Saša Ž.Drmanić, (05-2018), Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy: Elsevier, 196 (5), 16-30
Multivariate assessment of azo dyes' biological activity parametersJournal Article
Lipophilicity as key molecular descriptor of potential biological activity for selected derivatives of azo dyes was determined mathematically, by using relevant software packages and by reversed-phase thin-layer chromatography (RPTLC) on C18 and cyano modified carriers in mixtures of water/n-propanol and water/acetone. The obtained chromatographic parameters, RM0 and m, of the examined azo dyes were correlated with the standard measure of lipophilicity, log P, important pharmacokinetic predictors and selected toxicity parameters applying linear regression analysis. Thereby, good correlations for each applied system were obtained (average correlation coefficient, r, 0.944, 0.885 and 0.919). Also, the correlations between the studied parameters of azo dyes were examined applying two multivariate methods (Cluster Analysis and Principal Component Analysis). It was shown that the polarity of the substituent, and to a lesser extent its electronic effects has the greatest influence on the studied parameters of the azo dyes derivatives. Multivariate methods pointed out the similarity of the chromatographic retention constant, RM0, with the parameters of lipophilicity, unlike the chromatographic parameter m, which exhibits better agreement with the toxicity parameters.
Gyöngyi Vastag, Suzana Apostolov, Borko Matijević, Fathi Assaleh, (05-2018), Journal of Chromatography B: Elsevier, 1084 (1084), 141-149
QSRR approach in examining selected azo dyesJournal Article
Azo dyes as the most numerous and widely applied class of synthetic dyes in various industries at the same Azo dyes as the most numerous and widely applied class of synthetic dyes in various industries at the same time represent the great polluter of the aquatic systems and environment. Most of them are hydrophobic and resistant to degradation, but also they express diverse biological activity. The preliminary examinations of the bioactivity of the compounds include the estimation of their lipophilicity. The lipophilicity, as the key molecular descriptor for assuming an activity in a biological system for group of thiouracil azo dyes, was determined by the reversed-phase thin-layer chromatography (RPTLC18F254s) in different mixtures of water and (ethanol, i-propanol, dioxane, tetrahydrofurane) and mathematically using relevant software packages. The insight into the relationship between the chromatographic retention parameters, R0m and m of azo dyes with the partition coefficient log P, was attained by applying the linear regression analysis, Cluster analysis, and principal component analysis. All the applied methods have resulted in good agreements of the studied lipophilicity parameters of azo dyes. Also, these methods provided significant informations about the influence of the organic modifier on one side as well as the impact of the polarity and the electronic effect of substituent of examined dyes on their lipophilicity.
Gyöngyi Vastag, Suzana Apostolov, Borko Matijević, Fathi Assaleh, (10-2016), Journal of Liquid Chromatography & Related Technologies: Taylor & Francis Group, 39 (14), 674-681
Solvatochromism of Thiouracil Azo DyesJournal Article
A series of sixteen synthesized thiouracil azo dyes was obtained by condensation of arylazo acetoacetic esters with thiourea. Purified products were characterized by UV–Vis, FT–IR, 1H and 13C NMR spectroscopy. The UV–Vis absorption spectra of all synthesized compounds were recorded in nineteen solvents of different properties. The study and analysis of the spectral data of azo dyes generally indicate that the tautomeric equilibrium is shifted to the hydrazone tautomeric form in the solid state. Linear solvation energy relationships describe solvent influence on solvatochromism of the hydrazone form with the use of the Catalán model. Linear free energy relationships were applied in the form of single substituent parameter model to analyze substituent electronic effects on the spectral behavior of the compounds by Hammett’s equation. The correlations obtained with aid of theoretical calculations give insight into the influence of molecular conformation on the transmission of substituent effects, as well as different solvent–solute interactions.
Borko M. Matijević, Đenđi Đ. Vaštag, Suzana Lj. Apostolov, Fathi Assaleh, Aleksandar D. Marinković, Dušan Ž. Mijin, (05-2016), Journal of Solution Chemistry: Springer Nature, 45 (6), 885-906
A LFER Kinetic Study of The Reaction of 5-Substituted Orotic Acids with DiazodiphenylmethaneJournal Article
Linear free energy relationships (LFER) were applied to the kinetic data for the reaction of 5-substituted orotic acids, series 1, with diazodiphenylmethane (DDM) in N,N– dimethylformamide and compared with results obtained for 2-substituted benzoic acids, series 2. The correlation analysis of the kinetic data with σ substituent parameters was carried out using SSP (single substituent parameter) methods. From the sign and value of proportinality constant ρ, lower sensitivity to the substituent effect was obtained in series 1, 0.876, than in the series 2, 1.877. Evaluation of substituent “ortho-effect” was performed using the Charton model, which includes the steric substituent parameter, and Fujita and Nishioka’s model, which describes the total ortho-effect as contribution of ordinary polar effect, the ortho-steric and ortho-polar effects. Results of correlations, obtained by using the Charton model, showed highest contribution of the polar effect, 0.861 vs. 2.101, whereas the steric effect is of lowest significance, 0.117 vs. 0.055, for series 1 and 2, respectively. Also, a low negative value of coefficient with the steric effect, –0.08, obtained from the Fujita–Nishioka model indicated low steric effect, influencing a decrease of the reaction rate in series 1. The structural and substituent effects were also studied by using the density functional theory method, and together with kinetic data, it gave a better insight into the influence of the effect of both geometry and substituent on the π−electron density shift induced reactivity of investigated acids.
Fathi H. Assaleh, Aleksandar D. Marinković, Jasmina B. Nikolić, Saša Ž. Drmanić, Danijela Brković, Nevena Prlainović, Bratislav Ž. Jovanović, (04-2016), International Journal of Chemical Kinetics: Wiley, 48 (7), 367-378
Studying of physicochemical properties of newly synthesized uracil derivativesJournal Article
Uracil derivatives are potentially biologically active compounds, so the investigation of their physical and chemical properties is very important for their further application. In this work a series of newly synthesized derivatives of uracile was investigated by applying the spectrophotometric method. The absorption spectra were recorded in seventeen solvents with different properties. The effect of solvent was interpreted by Kamlet-Taft solvatochromic model. The dominance and the types of interactions that occur between the investigated derivatives and solvent were interpreted by applying the multiple linear correlation obtained values of absorption maxima and Hansen’s solvent parameters. In addition to the effect of solvent, the influence of substituents in the molecule on absorption spectra was studied by applying Hammett equation.
Borko M. Matijević, Đenđi Đ. Vaštag, Suzana Lj. Apostolov, Jadranka A. Tot, Fathi Assaleh, Aleksandar D. Marinković, (04-2015), Materials protection: Zastita Materijala, 56 (3), 279-288
Simultaneous Quantification of Mesalamine and Its Metabolite N-Acetyl mesalamine in human plasma by LC-MS/MS and its application to a bioequivalence studyJournal Article
Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used for simultaneous quantification of mesalamine and its metabolite N-acetyl mesalamine in human plasma with N-acetyl mesalamine D3 as an internal standard (IS). Chromatographic separation was performed on a Thermo, HyPURITY C18 (150 x 4.6 mm, 5 ïm) column with an isocratic mobile phase composed of 10 mM ammonium acetate and methanol in the ratio of 85:15 (%v/v), at the flowrate of 0.6 mL/min. The drug, metabolite and internal standard were extracted by liquid-liquid extraction. The method was validated over a linear concentration range of 2-1500 ng/mL for mesalamine and 10-2000 ng/ml for N-acetyl mesalamine, which demonstrated intra and inter-day precision ranging from 1.60 to 8.63% and 2.14 to 8.67% for mesalamine and 0.99 to 5.67% and 1.72 to 4.89% for N-acetyl mesalamine respectively. Similarly, the intra- and inter-day accuracy varied from 102.70 to 105.48% and 100.64 to 103.87% for mesalamine, 99.64 to 106.22% and 100.71 to 104.27% for N-acetyl mesalamine respectively. Both analytes were found to be stable throughout freeze–thawing cycles, bench top and postoperative stability studies. The method was successfully applied to support a bioequivalance study of healthy subjects.
Kanchanamala Kanala, Nagiat T. Hwisa, Babu Rao Chandu, Fathi H. Assaleh, K. Mukkanti, Prakash Katakam, Bala Sekhara Reddy Challa, (06-2014), Journal of Pharmaceutical Research International: SCIENCEDOMAINinternational, 4 (13), 1568-1590
Design of Experiment Assisted UV-Visible Spectrophotometric and RP-HPLC Method Development for Ambrisentan Estimation in Bulk and FormulationsJournal Article
Design of experiment (DOE) approach reinforces the robustness of the method being developed. This was employed for UV-visible (200-400 nm and 400-800 nm respectively) and RP-HPLC method development using C18 inertsil column and optimization of variables for ambrisentan (ABN) estimation in bulk and formulations. A two-level full factorial design assisted development of a visible spectroscopic method based on the principle of oxidation and coupling reaction of ABN with 3-methyl-2-benzothiazolinone hydrazone (MBTH reagent) in presence of FeCl3 to form bluish-green chromogen which is detectable in the visible range. second method estimates ABN in bulk and tablet dosage forms in the UV range using pH 7.4 phosphate buffer and the third one is a rapid, simple, stability indicating RP-HPLC method using a degassed mixture of orthophosphoric acid (OPA, 0.05M): acetonitrile (40:60) as mobile phase with water: acetonitrile (30:70) as diluent using PDA detector set at 264 nm for routine estimation of ABN in bulk and pharmaceutical dosage forms. Experimental design, data analysis and contour plots were developed using Minitab® 16.2.4 trial version (Minitab Inc). The percent assay of ABN detected by visible spectroscopy was 100.58±101.37% with RSD value 0.38%, by UV spectroscopy it was 99.1±99.8% with 0.5% RSD value and by RP-HPLC it was found 100.9%. The values of method validation parameters of three methodologies were found within the acceptance limits. The three methodologies could be regarded as specific, accurate, precise, with significant stability and robustness for routine estimation of ABN in bulk and tablet dosage forms.
Shanta K. Adiki, Prashanti M, Baishakhi Dey, Prakash Katakam, Fathi H. Assaleh, Nagiat T. Hwisa, Rajeev K. Singla, Babu R. Chandu, (06-2014), World Journal of Analytical Chemistry: Science and Education Publishing, 2 (2), 23-30
An Experimental Design Approach for Impurity Profiling of Valacyclovir-Related Products by RP-HPLCJournal Article
Impurity profiling has become an important phase of pharmaceutical research where both spectroscopic and chromatographic methods find applications. The analytical methodology needs to be very sensitive, specific, and precise which will separate and determine the impurity of interest at the 0.1% level. Current research reports a validated RP-HPLC method to detect and separate valacyclovir-related impurities (Imp-E and Imp-G) using the Box-Behnken design approach of response surface methodology. A gradient mobile phase (buffer: acetonitrile as mobile phase A and acetonitrile: methanol as mobile phase B) was used. Linearity was found in the concentration range of 50–150 μg/mL. The mean recovery of impurities was 99.9% and 103.2%, respectively. The %RSD for the peak areas of Imp-E and Imp-G were 0.9 and 0.1, respectively. No blank interferences at the retention times of the impurities suggest the specificity of the method. The LOD values were 0.0024 μg/mL for Imp-E and 0.04 μg/mL for Imp-G and the LOQ values were obtained as 0.0082 μg/mL and 0.136 μg/mL, respectively, for the impurities. The S/N ratios in both cases were within the specification limits. Proper peak shapes and satisfactory resolution with good retention times suggested the suitability of the method for impurity profiling of valacyclovir-related drug substances.
Prakash Katakam, Baishakhi Dey, Nagiat T. Hwisa, Fathi H. Assaleh, Babu R. Chandu, Rajeev K. Singla, Analava Mitra, (05-2014), Scientia Pharmaceutica: MDPI, 82 (3), 617-630
Solvent and structural effects in tautomeric 3-cyano-4-(substituted phenyl)-6-phenyl-2(1H)-pyridones: experimental and quantum chemical studyJournal Article
The tautomeric equilibria between 2-pyridone and 2-hydroxypyridine forms of methoxy, chloro, and nitro derivatives of 3-cyano-4-(2-, 3-, and 4-substituted phenyl)-6-phenyl-2(1H)-pyridones were evaluated from UV/Vis spectral data. Linear solvation energy relationships of Kamlet–Taft and Catalán-rationalized solvent have influence on tautomeric equilibria. Transmission of substituent effect was analyzed by the Hammett equation. Quantum chemical calculations were performed by density functional theory (B3LYP). The experimental data were interpreted with the aid of time-dependent density functional method. Electron density distribution was analyzed by Bader’s analysis. It was found that substituents of different electronic properties change the extent of conjugation, and affect intramolecular charge transfer character. Theoretical calculations and experimental results gave insight into the influence of the molecular conformation on the transmission of substituent effects, as well as on contribution of different solvent–solute interactions.
Ismail Ajaj, Jasmina Markovski, Jelena Marković, Maja Jovanović, Miloš Milčić, Fathi Assaleh, Aleksandar Marinković, (02-2014), Structural Chemistry: Springer Nature, 25 (4), 1257-1270
A Study on Antiurolithiatic Activity of Melia Azadirachta L. Aqueous Extract in RatsJournal Article
The objective was to investigate the antiurolithiatic activity of aqueous plant extract of Melia azadirachta using the zinc disc implantation model in male Wistar albino rats. A significant increase in urinary excretion of calcium, oxalate, magnesium and phosphate was observed after four weeks of implantation of zinc discs. After treatment with aqueous extract of Melia azadirachta caused a significant reduction (p < 0.001) in stone weight and urinary excretion of electrolytes in both the preventive and curative group of animals as compared to those of control groups. This explains the effect of the aqueous extract of Melia azadirachta in preventing urolithiasis (59%) and dissolving the pre-formed magnesium ammonium phosphate type of stones (46%). The possible mechanism could be due to the urinary stone-formation, lowering, antioxidant, diuretic, nephroprotective constituents present in Melia azadirachta. These results suggest the usefulness of aqueous plant extract of Melia azadirachta as an antiurolithiatic agent.
Nagiat T. Hwisa, Fathi H. Assaleh, Sumalatha Gindi, Fauzi ElMelad, Babu Rao Chandu, Prakash Katakam, (02-2014), American Journal of Pharmacological Sciences: Science and Education Publishing, 2 (1), 27-31
Synthesis and characterisation of starch tartrate and its application as novel disintegrant in telmisartan tabletsJournal Article
The aim of the present study was to synthesize potato starch (PS) derivatives of tartaric acid (TA) under semi-dry conditions and to evaluate the physicochemical properties as per official compendia requirements. Starch tartrate (ST) was synthesized by reacting PS (St–OH) and TA in semi-dry condition using sodium hypophosphite (SHP) as a catalyst. Further we have applied its use as disintegrant in directly compressed telmisartan tablets. The microscopic, spectroscopic (FTIR), thermal (DSC) and crystallographic (XRD) studies confirmed the formation of ST. No gelling was observed at 100°C but it was converted to a clear solution with a swelling index of 1.666 times. ST was found to have suitable compression properties required for directly compressible tablets. The tablets formulated employing ST (5–15% w/w) as disintegrant gave rapid disintegration and dissolution rates compared to those prepared using commercial superdisintegrants (sodium starch glycolate and crosscarmellose sodium). The optimized formulation showed disintegration time of 31 ± 3 s which is found superior to that of others. It is concluded that the synthesized ST could be employed as a promising disintegrant in dispersible tablet formulations.
Fathi H. Assaleh, Prakash Katakam, Ramesh Botcha, Babu Rao Chandu, Shanta Kumari Adiki, (11-2013), Starch/Stärke: John Wiley & Sons, 66 (3), 409-417
Stability indicating spectrophotometric methods of nelfinavir and their application to in-vitro bioequivalence testingJournal Article
The present investigation was aimed at developing the stability indicating spectrophotometric methods for the determination of nelfinavir mesylate (NEM) in pharmaceutical dosage forms. The stability of NEM was tested in various dissolution media maintained at ambient temperature and 37°C for 48 h. Stability studies of NEM in various media indicated that the drug was stable in 0.1M HC1 and pH 7.8 phosphate buffer, The max were found 201.4 and 212.0 nm for 0.1M HC1 and pH 7.8 phosphate buffers respectively with low coefficient of variation of < 5.11 %. The linearity of NEM was found in the range of 0.5 - 60 ug/mL for 0.1M HC1 and 0.5 - 40 ug/mL for pH 7.8 phosphate buffer. The validated methods were applied to determine NEM concentration in formulations. In-vitro dissolution testing indicated that the NEM was stable and drug release was uniform from tablet dosage forms. The optimized media could be employed to study the dissolution profiles of NEM in bioequivalence studies.
Fathi H. Assaleh, Shanta Kumari Adiki, Shaban G. Elosta, Fathi M. Asseid, Prakash Katakam, Babu Rao Chandu, (09-2013), Journal of Pharmaceutical and Scientific Innovation: Moksha Publishing House, 2 (5), 29-33
A Novel Visible Spectrophotometric Method for the Estimation of Betamethasone Using Oxidation ApproachJournal Article
A simple, sensitive, rapid and accurate spectrophotometric method was developed and validated for the estimation of betamethasone in bulk and pharmaceutical dosage forms. The method was based on the formation of bluish green chromophore with 0.04 % of sodium dichromate and concentrated sulphuric acid showing the absorption at 615 nm. The proposed method has permitted the quantification of betamethasone over linearity in the range of 5 - 30 μg/mL. The method was validated as per ICH guidelines.
Fathi Assaleh, Shaban G. Elosta, Fathi M. Asseid, Babu Rao Chandu, Prakash Katakam, (09-2013), Journal of Pharmaceutical and Scientific Innovation: Moksha Publishing House, 2 (5), 13-15
UV-Spectrophotometric Estimation of Acyclovir in Bulk and Pharmaceutical Dosage FormsJournal Article
Analytical method development being a vital part of pre formulation-formulation research and development obviates the need to develop reliable, effective, eco friendly and cost effective methodologies for routine analysis of active pharmaceutical ingredients. UV spectroscopy is one of the earliest, yet of wide applications in drug analysis in different stages of formulations and quality control; despite the availabilities of sophisticated chromatographic techniques and other hyphenated techniques. Current research attempts to develop simple, sensitive, accurate, precise and economical UV spectrophotometric methods for the routine analysis of acyclovir in bulk and pharmaceutical dosage forms using two separate alkaline media, 0.1N NaOH (method A) and 0.1N KOH (method B) and validate them as per ICH guidelines. In both the methods maximum absorbance was observed at 264 nm. Beer’s law was obeyed in the concentration of 2.5-40 μg / mL in method A and 2.5-30 μg / mL in method B with correlation coefficient of 0.999. The % recovery carried out by adding known amount of standard drug to pre-analyzed tablet solutions was 98.75 ± 0.52 % to 99.78 ± 0.69 % (method A) and 98.55 ± 0.31 % to 99.78 ± 0.22 % (method B). Intra and interday precision expressed in % RSD were 0.38 ± 0.01 and 0.27 ± 0.02 - 0.44 ± 0.01 respectively and the percent purity was 99.85 ± 0.05 %. The methods were validated statistically as per ICH guidelines and the results obtained were within the acceptance criteria for the parameters relating to linearity, accuracy, precision.
Narayana Raju Padala, Dey Baishakhi, Fathi H Assaleh, Prakash Katakam, Babu Rao Chandu, (08-2013), Journal of Pharmaceutical and Scientific Innovation: Moksha Publishing House, 2 (4), 40-43
Synthesis of Some Newer Nalidixic Acid Derivatives as Potent Antimicrobial AgentsJournal Article
A molecular manipulation efforts were made at β carbon of α, β unsaturated site of nalidixic acid by Michael addition, in expectation to get newer chemimanipulated derivatives with potent/modified antimicrobial spectrum. At the ends of chemimanipulative work, totally 5 derivatives were synthesized and characterized by spectral data. All the derivatives were screened for its antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aureginosa, and Proteus vulgaris at a concentration of 100μg/disc with the same dose of nalidixic acid as control by agar plate disc diffusion method. The results revealed that hydrazine substituted tricyclic derivatives exhibited potent antibacterial activity gram +ve rather than against gram –ve, however, potentiation were found to be against gram +ve and gram –ve bacteria.
Fathi H Assaleh, Babu Rao Chandu, Ramalingam Peraman, Prakash Katakam, (04-2013), Research and Reviews: Journal of Chemistry: RRJC, 2 (2), 17-19
Linear free energy relationships applied to the reactivity and the 13C NMR chemical shifts in 4–[[(substituted phenyl)imino]methyl] benzoic acidsJournal Article
Linear free energy relationships (LFER) were applied to the kinetic data and 13C NMR chemical shifts in 4-[[(substituted phenyl)imino]methyl]benzoic acids. The correlation analysis for the kinetic data and substituent-induced chemical shifts (SCS) with σ using single substituent parameter (SSP), as well as inductive (σI) and various resonance (σR) parameters using dual-substituent parameter (DSP), were carried out. The presented calculations account satisfactorily for the polar and resonance substituent effects having similar contributions at all carbons studied. Negative ρ values were found for several correlations (reverse substituent effect). Exceptionally good Hammett correlation of 13C NMR chemical shifts of azomethine carbon with electrophilic substituent constants σ+ indicates a significant resonance interaction in the aniline part of molecules. The conformations of investigated compounds have been studied by the use of DFT method, and together with 13C NMR chemical shifts and kinetic data, give a better insight into the influence of such a structure on the transmission of electronic substituent effects. New σ constants for substituted phenyliminomethyl group have been calculated.
Aleksandar D. Marinković, Bratislav Ž. Jovanović, Fathi H. Assaleh, Vlatka V. Vajs, Milan I. Juranić, (03-2012), Journal of Molecular Structure: Elsevier, 1011 (1), 158-165
13C NMR Substituent chemical shifts in 6-(4-substituted phenylimino) methyl uracilsJournal Article
The 13C NMR spectra of some 6-(4-substituted phenylimino) methyl uracils were measured in deuterated dimethyl sulfoxide (DMSO-d6). The observed 13 C substituent chemical shifts (SCS) were correlated with single and dual substituent parameters and analyzed using linear free energy relationships. The results were rationalized in terms of separate resonance and inductive contribution to the overall substituent effect, indicating to the occurrence of an apparent reverse polar effect.
Fathi H Assaleh, Aleksandar D. Marinković, Bratislav Ž. Jovanović, (11-2009), Univirsity Bulletin: Zawia University, 11 (2009), 17-28
Investigation of the reactivity of 4-pyrimidinecarboxylic, 6-hydroxy-4-pyrimidinecarboxylic and 5-hydroxyorotic acids with diazodiphenylmethane in various alcoholsJournal Article
Rate constants for the reaction of diazodiphenylmethane (DDM) with 4-pyrimidinecarboxylic, 6-hydroxy-4-pyrimidinecarboxylic and 5-hydroxyorotic acids were determined in twelve protic solvents at 30 °C using the well known UV-spectrophotometric method. The second order rate contants for the examined acids were correlated using the appropriate solvent parameters by the equation log k = log k0 + af(e) + bs * + cngH were f(e) is the Kirkwood function of relative permittivity [(e-l)/(2e + 1 )], s * is the Taft polar constant for the alkyl group R in the alcohol ROH, and nyH is themumber of hydrogen atoms in the (-position in the alcohol. The results obtained for the investigated acids were compared with the corresponding results for benzoic, 2- and 3-hydroxybenzoic acids and the influence of the structure of the investigated acids on the reactivity in hydroxylic solvents is discussed. It was also possible to evaluate and distinguish the specific and non-specific solvent effects and their influence on the reaction rate.
Fathi H. Assaleh, Aleksandar D. Marinković, Saša Ž. Drmanić, Bratislav Ž. Jovanović, (08-2007), Journal of Serbian Chemical Society: Serbian Chemical Society, 72 (3), 205-214
Carbon-13 substituent chemical shifts in N-1-p-substituted phenyl-5-methyl-4-carboxy uracilsJournal Article
The 13C NMR chemical shifts of seven N-1-p-substituted phenyl-5-methyl-4-carboxy uracils have been measured in deuterated dimethyl sulfoxide (DMSO-d6). The correlation analysis for the substituent-induced chemical shifts (SCS) with inductive (σI), and various resonance (σR) parameters were carried out through SSP (single substituent parameter), DSP (dual substituent parameter), and DSP-NLR (dual substituent parameter non-linear resonance) methods, as well as through multiple regression analysis. The presented calculation relative to the polar and resonance effects accounts satisfactorily for substituent effects at uracil carbon atoms. Negative ρ values were found for several correlations (reverse substituent effect).
Fathi H. Assaleh, Aleksandar D. Marinković, Bratislav Ž. Jovanović, Janos Csanádi, (05-2007), Journal of Molecular Structure: Elsevier, 833 (1), 53-57
Effect of substituents on the 13C chemical shifts of the azomethine carbon atom of N-(substituted phenylmethylene)-3- and -4-aminobenzoic acidsJournal Article
13C chemical shifts of the azomethine carbon atom for N-(substituted phenylmethylene)-3- and -4-aminobenzoic acids having a wide range of substituent effects, were determined in deuterated DMSO solution. Good Hammett correlations of the 13C NMR chemical shifts of azomethine carbons with electrophilic substituent constants for electron-donor substituents for both series of acids indicate an important resonance interaction of the substituents on the benzylidene ring with the azomethine carbon atom. On the other hand, good correlations of the 13C NMR chemical shifts of azomethine carbon atom of both series of acids with inductive substituent constants for electron-acceptor substituents in benzylidene ring indicates that the chemical shifts are influenced only by inductive effect of the substituents. The demand for electrons by the azomethine carbon atom in both investigated series have been compared, discussing the mode of transmission of substituent effects, both inductive and resonance, in relation to the geometry of investigated imines.
B. Ž. Jovanović, A. D. Marinković, F. H. Assaleh, (06-2005), Journal of Molecular Structure: Elsevier, 744 (747), 411-416
Kinetics of the reaction of 5-substituted orotic acids with diazodiphenylmethanJournal Article
Rate konstants for the reaction of eight 5-substituted orotic acids with diazodiphenylmethane (DDM) in dimethylformamide (DMF) were determined at 30 ºC by the known spectrophotometricmethod. The determined rate constants were correlated with the equations: logk2 = ασ1+βσR+h logk2 = ασ1+βσR+ψν+h to detect the presence and investigate the influence of both electrical and steric substituent effects. The obtained results show that the electrical effect (the localized – field and delocalized – resonance) is predominant and that the steric effect, althought present, is releatively small in this reaction.
Batislav Ž. Jovanović, Fathi H. Assaleh, Aleksandar D. Marinković, (08-2004), Journal of Serbian Chemical Society: Serbian Chemical Society, 69 (11), 949-953