RATIONAL DESIGN OF ANTIBACTERIAL THIENOPYRIMIDINES BY 2D-QSAR STUDY

QSAR studies were performed on a set of 43 analogs of thienopyrimidine using V-Life Molecular Design Suite (MDS 3.5) QSAR plus module by using Multiple Linear Regression (MLR) and Partial Least Squares (PLS) Regression methods against a gram positive (S.aureus) and a gram negative (E.coli) bacteria. MLR method has shown a very promising prediction results in both S.aureus and E.coli. QSAR model was generated by a training set of 34 molecules with correlation coefficient (r2) of 0.9849, 0.8719, significant cross validated correlation coefficient (q2) of 0.8881, 0.7811 and F test of  40.4301, 40.4768 respectively. In the selected descriptors, alignment independent descriptors such as T_C_C_7, T_N_O_3, T_2_N_1, T_N_O_1, T_O_O_7 and T_N_Cl_4 were the most important descriptors in predicting antibacterial activity

Rational Design of Antifungal 1,2,4-triazole derivatives by 2D-QSAR Study

2D-QSAR studies were performed on a set of 35 analogs of 1,2,4-triazole using V-Life Molecular Design Suite (MDS 3.5) QSAR plus module by using Multiple Linear Regression (MLR) and Partial Least Square (PLS) regression methods against fungal strain Aspergillus Niger (ATCC 6275). MLR and PLS have shown a very promising antifungal activity prediction results against A.Niger. QSAR models were (MLR and PLS) generated by a training set of 25 molecules with correlation coefficient (r2) of 0.7632, 0.7666, and F test of 16.1183, 22.9938 respectively. In the selected descriptors, alignment independent descriptors such as T_N_Cl_5, T_N_O_4, T_C_O_1, T_O_O_3 and G_C_O_1 were the most important descriptors in predicting antifungal activity

Design, synthesis, and biological evaluation of novel diclofenac analogs as promising anti-inflammatory agents

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesics and antipyretics in the treatment of pain, fever, and rheumatoid arthritis. Major side effect with treatment of NSAIDs is gastric irritation. 1,3,4-thiadiazole is an imperative scaffold since several of these derivatives are known to be associated with multiple biological activities such as anti-inflammatory, antibacterial, anti-cancer, anti-tubercular, and immunosuppressive. Literature survey reveals that certain compounds bearing this nucleus possess significant anti-inflammatory activity with reduced ulcerogenic effect. MATERIALS AND METHODS: In the present research work, we have synthesized thirteen 2-(2-[2,6-dichlorophenylamino] phenyl) acetohydrazide derivatives (4a–4m) and four 2,6-dichloro-N-(2-[6-phenylimidazo[2,1-b][1,3,4]thiadiazol-yl] methyl] phenyl) benzenamine derivatives (6a–6d) derived from diclofenac. All these newly synthesized compounds were screened for in vivo acute anti-inflammatory activity by carrageenan-induced rat paw edema method at a dose of 10 mg/kg bw. RESULTS AND DISCUSSION: Structures of these novel compounds were characterized based on their physicochemical and spectral analysis. Perusal of the activity data strongly suggests that compound 4d was most promising with significant anti-inflammatory activity, while moderate to good activity was observed for compounds 4a, 4c, g, 4i, and 4l. Among the imidazo (2,1-b) 1,3,4-thiadiazole series (6a–6d), compound 6b exhibited excellent anti-inflammatory activity, while compounds 6a, 6c and 6d displayed reasonably to good anti-inflammatory activity as compared to standard drug diclofenac. CONCLUSION: Among the series of synthesized compounds, two derivatives (4d and 6b) have displayed the most encouraging results and could be further exploited for developing newer anti-inflammatory agents with better efficacy and safety, which necessitates further investigations

Two-dimensional-quantitative structure-activity relationship studies of a novel series of diaryl furanone derivatives: An approach to design selective and effective cyclooxygenase-2 inhibitors

INTRODUCTION: Over a decade, a large number of selective cyclooxygenase-2 (COX-2) inhibitors with diverse chemical characteristics have been designed but only a few have emerged as drugs. MATERIALS AND METHODS: In the present study, two-dimensional-quantitative structure-activity relationship (2D-QSAR) studies were performed on a set of 43 novel derivatives of diaryl furanone using V-Life Molecular Design Suite (MDS 3.5) QSAR plus module using multiple linear regression (MLR) and Partial Least Square (PLS) regression methods against a COX-2 enzyme. RESULTS AND DISCUSSION: PLS method has displayed a very significant prediction results. QSAR model was generated by a training set of 33 molecules with correlation coefficient (r2) of 0.7695, cross-validated correlation coefficient (q2) of 0.5359 and F test of 23.3734. The estate contribution, chi, hydrophobic, and alignment-independent descriptors were major contributors. CONCLUSION: 2D-QSAR model result showed the positive contribution of oxygen atoms and negative contribution of rotatable bonds and distance between double bonds toward biological activity

Discovery of novel N-methyl carbazole tethered rhodanine derivatives asdirect inhibitors ofMycobacterium tuberculosisInhA

International audienc

Design, synthesis of 6-substituted-4-hydroxy-1-(2-substitutedalicyclicamino) acetyl)quinolin-2(1H)-one derivatives and evaluation of their in vitro anticancer activity

1167-1172The current research work deals with the design, synthesis of 6-substituted-4-hydroxy-1-(2-substitutedalicyclicamino)acetyl)quinolin-2(1H)-one derivatives and evaluation of their in vitro anticancer activity. Molecular docking studies of the title compounds have been carried out using Molegro Virtual Docker (MVD-2013, 6.0) software. The compounds exhibited well conserved hydrogen bonds with one or more amino acid residues in the active pocket of EGFRK tyrosine kinase domain (PDB ID: 1m17). The MolDock Score of compound (IIIc-3) is (−96.01) which is comparable to that of the standard ligand (−123.35) and Imatinib (−111.68). Most of the novel analogues of quinolin-2-one exhibit better affinity towards EGFRK protein than linomide (−81.17). These results show that the novel quinoline-2-one derivatives possess higher affinity than linomide towards the active site of the target protein EGFRK. The compounds have been synthesized using appropriate synthetic route. Some of the synthesized compounds have been characterized by UV, IR, 1H and 13C NMR and mass spectral data. Ten derivatives that have better MolDock score have been tested for their in vitro anticancer activity using KB (Oral cancer) cell line. Compound (IIIc-3) is found to be the most cytotoxic as compared to the other synthesized derivatives, with IC50 values of 1.07 µM/mL against KB(Oral cancer)cell line

Docking, synthesis, and characterization of novel heterocyclic ring system and their evaluation for mGlu8 receptor agonist as anticonvulsant agents

544-550This research work involves the synthesis of a series of substituted 1-(4-methoxy-1-phenyl/methyl-2-thioxo-1,2- dihydroquinolin-3-yl)ethanone [IVa/b(1-5)] derivatives by dimerization at third position and evaluation of their anticonvulsant activity. The starting material 3-acetyl-4-hydroxy-1-phenyl/methylquinolin-2(1H)-one Ia/b has been treated with P4S10:Al2O3 to yield compound 1-(4-hydroxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone (IIa/b). Compound IIa/b has been methylated to yield compound 1-(4-methoxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone (IIIa/b) which, on condensation with ketones forms dimers giving the title compounds IVa-b (1-5). All the synthesized compounds are satisfactorily characterized by spectral data. The in silico pharmacophore modeling of the title compounds has been performed using Molegro Virtual Docker (MVD-2007 software and mGlu8 is the target and in vivo anticonvulsant activity by phenylenetetrazole (PTZ) induced convulsion method. The results of docking have revealed that the synthesized compounds exhibit well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of metabotropic glutamate receptor mGluR8 complexed with (S)-3,4-dicarboxyphenylglycine (DCPG) (PDB ID:6E5V)LY341495 antagonist (PDB ID: 3MQ4). The MolDock Score of compound 2,6-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl)hepato-2,5-dien- 4-one (IVa-1) has been found to be −141.617. The in vivo anticonvulsant activity results show that compound 2,6-bis(4- methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl)hepato-2,5-dien-4-one (IVa-1), 2,7-bis(4-methoxy-1-phenyl-2-thioxo- 1,2-dihydroquinolin-3-yl)octa-2,6-dien-4,5-dione (IVa-2), 2,6-bis(4-methoxy-1-methyl-2-thioxo-1,2-dihydroquinolin-3- yl)hepato-2,5-dien-4-one (IVb-2) and (2E,6E)-2,6-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl) cyclohexanone (IVb-4) have been found to be most potent against pentylenetetrazole induced convulsion

Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents

Series of styryl hydrazine thiazole hybrids inspired from dehydrozingerone (DZG) scaffold were designed and synthesized by molecular hybridization approach. <i>In vitro</i> antimycobacterial activity of synthesized compounds was evaluated against <i>Mycobacterium tuberculosis</i> H₃₇Rv strain. Among the series, compound <b>6o</b> exhibited significant activity (MIC = 1.5 μM; IC₅₀ = 0.48 μM) along with bactericidal (MBC = 12 μM) and intracellular antimycobacterial activities (IC₅₀ = <0.098 μM). Furthermore, <b>6o</b> displayed prominent antimycobacterial activity under hypoxic (MIC = 46 μM) and normal oxygen (MIC = 0.28 μM) conditions along with antimycobacterial efficiency against isoniazid (MIC = 3.2 μM for INH-R1; 1.5 μM for INH-R2) and rifampicin (MIC = 2.2 μM for RIF-R1; 6.3 μM for RIF-R2) resistant strains of Mtb. Presence of electron donating groups on the phenyl ring of thiazole moiety had positive correlation for biological activity, suggesting the importance of molecular hybridization approach for the development of newer DZG clubbed hydrazine thiazole hybrids as potential antimycobacterial agents

Docking, synthesis, and characterization of novel heterocyclic ring system and their evaluation for mGlu8 receptor agonist as anticonvulsant agents

This research work involves the synthesis of a series of substituted 1-(4-methoxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone [IVa/b(1-5)] derivatives by dimerization at third position and evaluation of their anticonvulsant activity. The starting material 3-acetyl-4-hydroxy-1-phenyl/methylquinolin-2(1H)-one Ia/b has been treated with P4S10:Al2O3 to yield compound 1-(4-hydroxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone (IIa/b). Compound IIa/b has been methylated to yield compound 1-(4-methoxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone (IIIa/b) which, on condensation with ketones forms dimers giving the title compounds IVa-b (1-5). All the synthesized compounds are satisfactorily characterized by spectral data. The in silico pharmacophore modeling of the title compounds has been performed using Molegro Virtual Docker (MVD-2007 software and mGlu8 is the target and in vivo anticonvulsant activity by phenylenetetrazole (PTZ) induced convulsion method. The results of docking have revealed that the synthesized compounds exhibit well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of metabotropic glutamate receptor mGluR8 complexed with (S)-3,4-dicarboxyphenylglycine (DCPG) (PDB ID:6E5V)LY341495 antagonist (PDB ID: 3MQ4). The MolDock Score of compound 2,6-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl)hepato-2,5-dien-4-one (IVa-1) has been found to be −141.617. The in vivo anticonvulsant activity results show that compound 2,6-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl)hepato-2,5-dien-4-one (IVa-1), 2,7-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl)octa-2,6-dien-4,5-dione (IVa-2), 2,6-bis(4-methoxy-1-methyl-2-thioxo-1,2-dihydroquinolin-3-yl)hepato-2,5-dien-4-one (IVb-2) and (2E,6E)-2,6-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl) cyclohexanone (IVb-4) have been found to be most potent against pentylenetetrazole induced convulsion

Single robust RP-HPLC analytical method for quantification of curcuminoids in commercial turmeric products, Ayurvedic medicines, and nanovesicular systems

<p>A single robust reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated as per International Conference on Harmonization guidelines for the accurate quantification of curcuminoids in commercial turmeric products, Ayurvedic medicines, and nanovesicular systems. The proposed chromatographic method was found to be specific, linear (<i>r</i>² ≥ 0.999), precise at intra- and inter-day levels (percentage relative standard deviation <2.0%), accurate (percentage recovery 99.14–102.29%), and robust. The limits of detection and quantification were found to be 7.40 and 24.70 ng mL⁻¹ for curcumin, 9.24 and 30.80 ng mL⁻¹ for demethoxycurcumin, and 6.48 and 21.61 ng mL⁻¹ for bisdemethoxycurcumin, respectively. Among different commercial turmeric products and Ayurvedic medicines tested, the contents of curcumin (3.54 ± 0.06–25.8 ± 0.08 mg g⁻¹), demethoxycurcumin (1.28 ± 0.02–9.97 ± 0.03 mg g⁻¹), and bisdemethoxycurcumin (0.50 ± 0.01–5.97 ± 0.01 mg g⁻¹) varied significantly. The developed method was effectively applied to the determination of encapsulation efficiency of curcuminoids (ranged between 84.33 ± 3.50 and 96.59 ± 2.53%) in the nanovesicular systems. In conclusion, the reported method is suitable for the analysis of curcuminoids in a wide variety of turmeric products and used for the quality control of products that contain curcuminoids.</p