Karthikeyan Chandrabose

Publications

• 1.50

  Impact points

  Synthesis, in silico metabolic and toxicity prediction of some novel imidazolinones derivatives as potent anticonvulsant agents.

  N S Hari Narayana Moorthy, Vipin Saxena, C Karthikeyan, Piyush Trivedi

  Journal of enzyme inhibition and medicinal chemistry. 06/2011; 27(2):201-7.

  A series of 1,2,4-trisubstituted 5-imidazolinone derivatives were synthesized by Erlenmeyer condensation of benzoylglycine (hippuric acid) with different aldehydes in the presence of sodium acetate and acetic anhydride. The derivatives of the compounds were prepared by condensation of some known sul... [more] A series of 1,2,4-trisubstituted 5-imidazolinone derivatives were synthesized by Erlenmeyer condensation of benzoylglycine (hippuric acid) with different aldehydes in the presence of sodium acetate and acetic anhydride. The derivatives of the compounds were prepared by condensation of some known sulpha drugs with 5-oxazolone derivatives. The anticonvulsant activity of the compounds was determined by the protection of pentylenetetrazole-induced convulsions that was ranged from 10 to 60%. The compounds with p-OCH(3), p-OH and o-Cl substitutions in the phenyl ring on 4(th) position of the imidazolinone ring exhibited good anticonvulsant activity. In silico metabolic and toxicity studies showed that all the compounds in the series are not likely to exhibit toxicity except the compounds IIIa, IIIb, VIa and VIb, that is predicted to show 29% mutagenicity and 53% irritation in comparison to the other compounds. The predicted lethal effect and hERG toxicity of the compounds showed that IIa, IVa, Va and Vb might be toxic at higher concentrations. The results successfully establish the synthesized imidazolinone derivatives as novel compounds with anticonvulsant properties, low predicted cardiotoxicity and lethal effects thus can be promising leads for further development as novel anticonvulsants.

• Synthesis of Some Coumarinyl Chalcones and their Antiproliferative Activity Against Breast Cancer Cell Lines

  Kuldeep Patel, Chandrabose Karthikeyan, Viswas Raja Solomon, N.S. Hari Narayana Moorthy, Moorthy, Hoyun Lee, Kapendra Sahu, Girdhar Singh Deora, Piyush Trivedi

  Letters in Drug Design & Discovery. 01/2011; 8:308-311.

  A series of coumarinyl chalcones derivatives were synthesized and evaluated for their antiproliferative activities on three different breast cancer cell lines (MDA-MB231, MDA-MB468, MCF7) and one non-cancer breast epithelial cell line (184B5). The coumarinyl derivatives exhibited anticancer activity... [more] A series of coumarinyl chalcones derivatives were synthesized and evaluated for their antiproliferative activities on three different breast cancer cell lines (MDA-MB231, MDA-MB468, MCF7) and one non-cancer breast epithelial cell line (184B5). The coumarinyl derivatives exhibited anticancer activity against breast cancer cell lines at a micromolar range. A structure-activity relationship (SAR) analysis was performed by studying the effect of substituents on their anti-proliferative activities. One of the compound 3i bearing methoxy substitutions at the R1, R2 and R3 positions of the phenyl ring showed comparable potency to the reference drug cisplatin as well as a two-fold higher selectivity for the breast cancer cell lines than 184B5 cells.
• 1.64

  Impact points

  3D QSAR of aminophenyl benzamide derivatives as histone deacetylase inhibitors.

  Mahipal, Om Prakash Tanwar, C Karthikeyan, N S Hari Narayana Moorthy, Piyush Trivedi

  Medicinal chemistry (Shāriqah (United Arab Emirates)). 10/2010; 6(5):277-85.

  The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 48 aminophenyl benzamide derivatives reported for Histone Deacetylase (HDAC) inhibition using PHASE module of Schrodinger software. A five point pharmacophore mo... [more] The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 48 aminophenyl benzamide derivatives reported for Histone Deacetylase (HDAC) inhibition using PHASE module of Schrodinger software. A five point pharmacophore model consisting of two aromatic rings (R), two hydrogen bond donors (D) and one hydrogen bond acceptor (A) with discrete geometries as pharmacophoric features was developed and the generated pharmacophore model was used to derive a predictive atom-based 3D QSAR model for the studied dataset. The obtained 3D QSAR model has an excellent correlation coefficient value (r(2)=0.99) along with good statistical significance as shown by high Fisher ratio (F=631.80). The model also exhibits good predictive power confirmed by the high value of cross validated correlation coefficient (q(2) = 0.85). The QSAR model suggests that hydrophobic character is crucial for the HDAC inhibitory activity exhibited by these compounds and inclusion of hydrophobic substituents will enhance the HDAC inhibition. In addition to the hydrophobic character, hydrogen bond donating groups positively contributes to the HDAC inhibition whereas electron withdrawing groups has a negative influence in HDAC inhibitory potency. The findings of the QSAR study provide a set of guidelines for designing compounds with better HDAC inhibitory potency.
• 2.65

  Impact points

  A new approach for PEGylation of dendrimers.

  Hemant Khambete, Surya P Gautam, C Karthikeyan, Suman Ramteke, N S Hari Narayana Moorthy, Piyush Trivedi

  Bioorganic & medicinal chemistry letters. 07/2010; 20(14):4279-81.

  Dendrimers have emerged as one of the most interesting themes for researchers as a result of unique functional architecture and macromolecular characteristics. The reported methods of PEGylation are very time consuming and required multisteps for synthesis. In present work we have synthesized PEGyla... [more] Dendrimers have emerged as one of the most interesting themes for researchers as a result of unique functional architecture and macromolecular characteristics. The reported methods of PEGylation are very time consuming and required multisteps for synthesis. In present work we have synthesized PEGylated polyamidoamine (PAMAM) dendrimers using epichlorohydrin as a linker. The PEGylated dendrimers were evaluated for color reaction UV, IR and NMR studies and compared with standard data.
• 1.50

  Impact points

  Design, synthesis, cytotoxic evaluation, and QSAR study of some 6H-indolo[2,3-b]quinoxaline derivatives.

  N S Hari Narayana Moorthy, C Karthikeyan, Piyush Trivedi

  Journal of enzyme inhibition and medicinal chemistry. 03/2010; 25(3):394-405.

  In the pathway of anticancer drug development, we designed and synthesized some 6H-indolo[2,3-b]quinoxaline derivatives (which act as DNA intercalators) by structural modification. The structure of the 6H-indolo[2,3-b]quinoxaline derivatives was confirmed by IR, NMR, Mass and elemental analysis. The... [more] In the pathway of anticancer drug development, we designed and synthesized some 6H-indolo[2,3-b]quinoxaline derivatives (which act as DNA intercalators) by structural modification. The structure of the 6H-indolo[2,3-b]quinoxaline derivatives was confirmed by IR, NMR, Mass and elemental analysis. The compounds (IDQ-5, IDQ-10, IDQ-11, IDQ-13, and IDQ-14) exhibited significant in vitro activity against a human leukemia (HL-60) cell line. The QSAR derived for modeling the cytotoxic activity of 6H-indolo[2,3-b]quinoxaline derivatives suggests that candidate structures for increased cytotoxic potency should incorporate cyclic substituents or substituents with primary carbon atoms.
• 1.64

  Impact points

  QSAR study on hetaryl imidazoles: a novel dual inhibitor of VEGF receptors I and II.

  Asha Patel, C Karthikeyan, N S H N Moorthy, P Trivedi

  Medicinal chemistry (Shāriqah (United Arab Emirates)). 01/2010; 6(1):24-9.

  A series of hetaryl imidazoles with VEGF receptors I and II inhibitory activities was subjected to QSAR analysis employing molecular descriptors calculated using QSAR software Dragon. Quantitative models of good statistical significance were formulated for both the activities through stepwise multip... [more] A series of hetaryl imidazoles with VEGF receptors I and II inhibitory activities was subjected to QSAR analysis employing molecular descriptors calculated using QSAR software Dragon. Quantitative models of good statistical significance were formulated for both the activities through stepwise multiple linear regression using the method of least squares and the generated models were evaluated for predictive ability employing cross validation procedure following a leave-one-out scheme. The interpretation of the QSAR models indicated that VEGF receptor II inhibitory activity of the title compounds is influenced by the number of hydrogen acceptor atoms and benzyl groups in the molecule whereas VEGF receptor I inhibitory activity is influenced by benzyl and aromatic functionalities and dipoles in the molecule. Furthermore, the QSAR model derived for Model for VEGF receptor II (cell based ELISA) inhibitory activity highlighted that electron withdrawing groups are beneficial and lipophilic moieties are detrimental to the activity.

• QSAR studies on dihydro-alkoxy-benzyl-oxopyrimidines (DABOs) derivatives, a new series of potent, broad-spectrum non-nucleoside reverse transcriptase inhibitors

  Laxmi Gupta, Asha Patel, Chandrabose Karthikeyan and Piyush Trivedi

  Journal of Current Pharmaceutical Research. 01/2010;

  Objective: Non-nucleoside reverse transcriptase is an essential enzyme required for replication of the acquired immunodeficiency syndrome virus. It is a potent target for anti- HIV therapy. A QSAR study is performed on the series 5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-... [more] Objective: Non-nucleoside reverse transcriptase is an essential enzyme required for replication of the acquired immunodeficiency syndrome virus. It is a potent target for anti- HIV therapy. A QSAR study is performed on the series 5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones belonging to dihydro-alkoxy-benzyl-oxopyrimidines (DABOs) derivatives in order to analyze the physicochemical requirements of non-nucleoside reverse transcriptase inhibitors and to provide structural insight into the binding mode of the molecules to the enzyme. This will help in the design of these molecules as non-nucleoside reverse transcriptase inhibitors and predicting the inhibitory activity of the newly designed analogues.Materials & Methods: All the derivatives in the series were sketched using ChemDraw module of ChemOffice 2001 and the sketched structures were subsequently used for the calculation of molecular descriptors available in QSAR software dragon. Empirical, constitutional, topological and functional group descriptors for all molecules were calculated using QSAR software dragon 2005 and correlation between the biological activity and molecular descriptors was found through forward stepwise multiple regression analysis using the method of least squares adopted by statistical program VALSTAT.Results: The generated QSAR models revealed that Hy (hydrophilic factors), MSD (mean square distance index), nCrHR (number of ring quaternary), RBN (total number of rotatable bonds) and ARR (aromatic ratio) descriptors have good correlation to the non-nucleoside reverse transcriptase inhibitors activity.Conclusion: The results obtained by regression analysis indicated that Hy (hydrophilic Factors), which regulates the hydrophilicity of the molecules, is negatively contributing to inhibitory activity thus; enhancement of inhibitory activity can be achieved by substitution with more hydrophobic substituents. Positive contribution of RBN (total number of rotatable bonds) specifies that substitution with groups, which are having rotatable bonds, will impart positive influence on activity. MSD, Mean square distance index (balaban) is contributing negatively to the activity, which suggests that substituents have greater branching will improve inhibitory activity.
• 1.64

  Impact points

  Synthesis, cytotoxic evaluation and in silico pharmacokinetic prediction of some benzo[a]phenazine-5-sulfonic acid derivatives.

  N S Hari Narayana Moorthy, C Karthikeyan, Piyush Trivedi

  Medicinal chemistry (Shāriqah (United Arab Emirates)). 11/2009; 5(6):549-57.

  Cancer is one of the life threatening diseases and the development of novel anticancer molecules is limited by many reasons. In the present investigation, some novel benzo[a]phenazine-5-sulfonic acid derivatives as DNA intercalator was designed with optimized pharmacokinetic features for cancer trea... [more] Cancer is one of the life threatening diseases and the development of novel anticancer molecules is limited by many reasons. In the present investigation, some novel benzo[a]phenazine-5-sulfonic acid derivatives as DNA intercalator was designed with optimized pharmacokinetic features for cancer treatment. The compounds with desired pharmacokinetic profile were synthesized and structurally characterized. Cytotoxic activity study against HL-60 tumor cell lines shows that 10-dimethyl carboxamido derivative of benzo[a]phenazine-5-sulfonic acid is found to be the most active in the series with cytotoxic activity (IC(50) = 19 microM) comparable to cisplatin (IC(50) = 7 microM). The study concluded that the novel benzo[a]phenazine-5-sulfonic acid derivatives were found to have enhanced DNA binding affinity and exhibited significant activity in vitro against HL-60 cell lines. This work will also guide for further development of effective DNA intercalators for cancer treatment.
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  Impact points

  Quantitative Structure Activity Relationship Studies of Piperazinyl Phenylalanine Derivatives as VLA-4/VCAM-1 Inhibitors.

  Dinesh Bhargava, C Karthikeyan, N S H N Moorthy, Piyush Trivedi

  Medicinal chemistry (Shariqah (United Arab Emirates)). 10/2009;

  QSAR study was carried out for a series of piperazinyl phenylalanine derivatives exhibiting VLA-4/VCAM-1 inhibitory activity to find out the structural features responsible for the biological activity. The QSAR study was carried out on V-life Molecular Design Suite software and the derived best QSAR... [more] QSAR study was carried out for a series of piperazinyl phenylalanine derivatives exhibiting VLA-4/VCAM-1 inhibitory activity to find out the structural features responsible for the biological activity. The QSAR study was carried out on V-life Molecular Design Suite software and the derived best QSAR model by partial least square (forward) regression method showed 85.67% variation in biological activity. The statistically significant model with high correlation coefficient (r2=0.85) was selected for further study and the resulted validation parameters of the model, crossed squared correlation coefficient (q2=0.76 and pred_r2=0.42) show the model has good predictive ability. The model showed that the parameters SaaNEindex, SsClcount slogP,and 4PathCount are highly correlated with VLA-4/VCAM-1 inhibitory activity of piperazinyl phenylalanine derivatives. The result of the study suggests that the chlorine atoms in the molecule and fourth order fragmentation patterns in the molecular skeleton favour VLA-4/VCAM inhibition shown by the title compounds whereas lipophilicity and nitrogen bonded to aromatic bond are not conducive for VLA-4/VCAM-1 inhibitory activity.
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  Impact points

  QSAR study of substituted 2-pyridinyl guanidines as selective urokinase-type plasminogen activator (uPA) inhibitors.

  C Karthikeyan, N S Hari Narayana Moorthy, Piyush Trivedi

  Journal of enzyme inhibition and medicinal chemistry. 12/2008;

  A quantitative structure-activity relationship analysis was conducted on two different series of pyridinylguanidines acting as inhibitors of urokinase-type plasminogen activator using QuaSAR descriptors of molecular modeling software MOE. Multiple linear regression analysis following a stepwise sche... [more] A quantitative structure-activity relationship analysis was conducted on two different series of pyridinylguanidines acting as inhibitors of urokinase-type plasminogen activator using QuaSAR descriptors of molecular modeling software MOE. Multiple linear regression analysis following a stepwise scheme was employed to generate QSARs that relate molecular descriptors to uPA inhibitory activity data of the title compounds. Among the several QSARs generated by MLR analysis, the best models were selected on the basis of their statistical significance and predictive potential. The interpretation of the selected QSAR models suggest that uPA inhibitory activity of compounds in series 1 is influenced by their molecular shape, molecular flexibility and halogen atoms in the molecule whereas the uPA inhibitory potency of compounds in series 2 is dependent on molecular lipophilicity, number of double bonds and spatial orientation of bulky substituents in the molecule.
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  Impact points

  Quantitative structure activity analysis of 2-alkoxydihydrocinnamates as PPARalpha/gamma dual agonist.

  P Manoj Kumar, R Hemalatha, S C Mahajan, C Karthikeyan, N S Hari Narayana Moorthy, Piyush Trivedi

  Medicinal chemistry (Shāriqah (United Arab Emirates)). 06/2008; 4(3):273-7.

  To optimize the physiochemical properties of 2-alkoxydihydrocinnamates as PPARalpha/gamma dual agonist, a quantitative structure activity relationship, Hansch approach was made using combination of various thermodynamic, electronic and spatial descriptors. Several regression expressions are obtained... [more] To optimize the physiochemical properties of 2-alkoxydihydrocinnamates as PPARalpha/gamma dual agonist, a quantitative structure activity relationship, Hansch approach was made using combination of various thermodynamic, electronic and spatial descriptors. Several regression expressions are obtained using multiple linear regression analysis. The best QSAR model is further validated by leave-one-out cross validation method. Analyses of results from the present QSAR study suggest that for favorable dual PPARalpha/gamma agonist activity electronic property of the substituents in hydrophobic tail phenyl ring plays a key role. The contribution of Hammett constant and dipole moment in the models deduced the importance of electron withdrawing substituents for dual activity. Additionally the study also indicates that bulky substituents in head acid moiety not confer selectivity towards the PPAR activity. Thus the QSAR study brings important structural insight to aid the design of dual PPARalpha/gamma receptor agonist.
• 1.70

  Impact points

  Quantitative structure-activity relationships of selective antagonists of glucagon receptor using QuaSAR descriptors.

  Palanivelu Manoj Kumar, Chandrabose Karthikeyan, Narayana Subbiah Hari Narayana Moorthy, Piyush Trivedi

  Chemical & pharmaceutical bulletin. 12/2006; 54(11):1586-91.

  In the present paper, quantitative structure activity relationship (QSAR) approach was applied to understand the affinity and selectivity of a novel series of triaryl imidazole derivatives towards glucagon receptor. Statistically significant and highly predictive QSARs were derived for glucagon rece... [more] In the present paper, quantitative structure activity relationship (QSAR) approach was applied to understand the affinity and selectivity of a novel series of triaryl imidazole derivatives towards glucagon receptor. Statistically significant and highly predictive QSARs were derived for glucagon receptor inhibition by triaryl imidazoles using QuaSAR descriptors of molecular operating environment (MOE) employing computer-assisted multiple regression procedure. The generated QSAR models revealed that factors related to hydrophobicity, molecular shape and geometry predominantly influences glucagon receptor binding affinity of the triaryl imidazoles indicating the relevance of shape specific steric interactions between the molecule and the receptor. Further, QSAR models formulated for selective inhibition of glucagon receptor over p38 mitogen activated protein (MAP) kinase of the compounds in the series highlights that the same structural features, which influence the glucagon receptor affinity, also contribute to their selective inhibition.
• 2.65

  Impact points

  QSAR analysis of some 5-amino-2-mercapto-1,3,4-thiadiazole based inhibitors of matrix metalloproteinases and bacterial collagenase.

  Ashutosh Jamloki, C Karthikeyan, N S Hari Narayana Moorthy, P Trivedi

  Bioorganic & medicinal chemistry letters. 08/2006; 16(14):3847-54.

  A quantitative structure-activity relationship (QSAR) study has been performed on 5-amino-2-mercapto-1,3,4-thiadiazole based inhibitors of matrix metalloproteinases (MMPs) and a bacterial collagenase known as Clostridium histolyticum collagenase (ChC) to understand the structural features influencin... [more] A quantitative structure-activity relationship (QSAR) study has been performed on 5-amino-2-mercapto-1,3,4-thiadiazole based inhibitors of matrix metalloproteinases (MMPs) and a bacterial collagenase known as Clostridium histolyticum collagenase (ChC) to understand the structural features influencing the affinity of these inhibitors towards the enzyme. The compounds in the selected series were characterized by topological and fragmental descriptors calculated using QuaSAR module of molecular operating environment (MOE). An indicator variable was also assigned to account for the presence of amide function in vicinity of sulfonamide group in the parent structure. Correlations between different inhibitory activities and calculated predictor variables were established through stepwise multiple regression employing the method of least squares. The results of the study indicates that MMP inhibitory activity of 5-amino-2-mercapto-1,3,4-thiadiazoles can be successfully explained in terms of topology of the molecule. The obtained correlations also suggest that increase in the number of fluorine atoms in the aromatic ring will augment inhibitory activity of these molecules against all the MMPs probably by virtue of hydrogen bond interaction with some complementary groups in the active site of the enzymes. One prime requirement for better inhibition of MMPs (except for MMP-1) and ChC identified from the present study is the presence of amide function in vicinity of sulfonamide group in the parent structure as suggested by the presence of indicator variable in almost all correlations. While MMP-1 and ChC inhibitory activity of the compounds studied is shown to be dependent on Kier's first order carbon valence molecular connectivity index indicating that increase in branching and presence of heteroatoms in the molecule will improve the MMP-1 and ChC inhibitory potency of 5-amino-2-mercapto-1,3,4-thiadiazoles, correlations derived for other enzymes (MMP-2, MMP-8, MMP-9) are quite similar. In addition to the number of fluorine atoms and presence of indicator variable, MMP-2, MMP-8 and MMP-9 inhibitory activity of 5-amino-2-mercapto-1,3,4-thiadiazoles is found to be dependent on Kier's alpha modified index of third order in such a way that infer, terminally branched functions will increase the affinity of these molecules to the MMPs.

• New spectrophotometric methods applied to the simultaneous determination of diclofenac potassium and tizanidine

  Sanjay Kumar R, C Karthikeyan, N Moorthy, P Trivedi

  Indian Journal of Pharmaceutical Sciences. 01/2006;

  Simple, sensitive, and specific spectrophotometric methods were developed and validated for quantitation of diclofenac potassium and tizanidine in tablet dosage form. Three new analytical methods were developed based on the simultaneous estimation of drugs in a binary mixture without previous separa... [more] Simple, sensitive, and specific spectrophotometric methods were developed and validated for quantitation of diclofenac potassium and tizanidine in tablet dosage form. Three new analytical methods were developed based on the simultaneous estimation of drugs in a binary mixture without previous separation. In multiwavelength technique, the binary mixture was determined by mixed standards and three sampling wavelengths of 277 nm, 295 nm (isobestic point), and 320 nm. In simultaneous equation method, the drugs were determined by using the absorptivity values of diclofenac potassium and tizanidine at selected wavelengths, viz., 277 nm and 320.3 nm. The standard deviation value for the validation parameters was found to be between 0.08 and 0.68 for multiwavelength technique and between 0.069 and 1.23 for simultaneous equation method. The graphical absorbance ratio method was performed by absorbances at 277 nm, 295 nm (isobestic point), and 320.4 nm of their mixture. These three methods are simple, accurate, and rapid, and they require no preliminary separation and can therefore be used for routine analysis of both drugs in quality control laboratories.
• 2.65

  Impact points

  QSAR modelling of HIV-1 reverse transcriptase inhibition by benzoxazinones using a combination of P_VSA and pharmacophore feature descriptors.

  S Balaji, C Karthikeyan, N S Hari Narayana Moorthy, Piyush Trivedi

  Bioorganic & medicinal chemistry letters. 01/2005; 14(24):6089-94.

  In pursuit of better anti-HIV drugs, a quantitative structure-activity relationship analysis using a novel set of 2D descriptors was performed on a series of HIV-1 reverse transcriptase inhibitory benzoxazinones. The QSAR models derived from the above mentioned descriptors were found to be statistic... [more] In pursuit of better anti-HIV drugs, a quantitative structure-activity relationship analysis using a novel set of 2D descriptors was performed on a series of HIV-1 reverse transcriptase inhibitory benzoxazinones. The QSAR models derived from the above mentioned descriptors were found to be statistically significant and exhibited superior predictive power. The results of the study justify the application of the descriptors for exploring the binding mode of the benzoxazinones to the enzyme.

• Simultaneous quantitative determination of zidovudine and nevirapine in human plasma using isocratic, reverse phase high performance liquid chromatography

  Vibhuti Kabra, Vivek Agrahari, Chandrabose Karthikeyan, Piyush Trivedi

  Tropical Journal of Pharmaceutical Research (ISSN: 1596-5996) Vol 8 Num 1.

  Purpose: To develop a sensitive and rapid reverse phase high performance liquid chromatography (HPLC) method for the measurement of the levels of zidovudine (ZVD) and nevirapine (NVP) in human plasma. Methods: Standard stock solutions for HPLC analysis were prepared by dissolving ZVD and NVP in meth... [more] Purpose: To develop a sensitive and rapid reverse phase high performance liquid chromatography (HPLC) method for the measurement of the levels of zidovudine (ZVD) and nevirapine (NVP) in human plasma. Methods: Standard stock solutions for HPLC analysis were prepared by dissolving ZVD and NVP in methanol. In the HPLC measurement, sample detection was carried out at 246 nm using an ultraviolet (UV)-photo diode array (PDA) detector. Plasma sample pretreatment consisted of protein precipitation extraction with methanol. The compounds were separated using a mobile phase consisting of a pH 3.0 solution (obtained by adjusting the pH of water with orthophosphoric acid): acetonitrile (73:27 v/v) on a Phenomenex LUNA C18, column (250×4.6 mm i.d., 5µm) at a flow rate of 0.9 mL min. The total run time for the assay was 10.2 min-1 . The method was validated over the range of 300-9600 ng mL-1 and 200-6400 ng mL-1 for ZVD and NVP, respectively. Results: The lowest limits of quantification (LLOQ) and of detection (LOD) were 300 and 63 ng mL-1 for ZVD and 200 and 17 ng mLfor NVP, respectively. The method was found to be accurate, with accuracy ranging from -10.92 to +9.57 % and precise, with intra-day, inter-day as well as analyst to analyst precision of 0.68 to 9.38 %. Extraction recoveries of the drugs from plasma were 91.39, 95.01, 89.51 % for ZVD and 90.93, 93.26, 92.13 % for NVP, for LQC (low quality control), MQC (medium quality control) and HQC (high quality control) samples, respectively. Stability data revealed that the drugs were stable in plasma under various test conditions. Conclusion: This assay can be suitably used for the determination of zidovudine (ZVD) and nevirapine (NVP) in human plasma and should be useful in HIV clinical trials and clinical therapeutic drug monitoring (TDM) programs. It would also be potentially useful in the determination of pharmacokinetic profiles and in bioequivalence studies in HIV research.