Mukesh C. Sharma

Synthesis, docking studies and antioxidant activity of some chalcone and aurone derivatives

Chalcones and aurones are found to possess high antioxidant activity. They are known to inhibit tyrosinase enzyme involved in synthesis of melanin. A series of substituted chalcones and aurones have been synthesized and tested for their antioxidant activity. Postulated structures of the newly synthesized compounds are in agreement with their IR, 1H NMR and MS. The docking study of this series of compounds was performed on crystal structure of tyrosinase from Bacillus megaterium using VlifeMDS 3.0 software. Antioxidant activity data obtained from four methods, i.e., DPPH free radical scavenging assay, iron chelating assay, reducing power assay and hydrogen peroxide scavenging assay, indicate that the activity increased with dimethylamino group on position 4/4′ of ring B as evident from the significant activities of SB7 and SB8 in case of chalcones and aurones, respectively. The poor activities of SB4 and SB5 in DPPH scavenging ability and reducing power assays could be because of presence of chloro group on B-ring. Furthermore, the activity is facilitated with the presence of hydroxyl group on A-ring (preferably on position 5/5′) in both chalcones and aurones.

QSAR studies on imidazopyridazine derivatives as PfPK7 inhibitors

Quantitative structure–activity relationship (QSAR) studies were carried out on a series of 35 recently synthesised imidazopyridazine derivatives to investigate the structural requirements of their inhibitory activity against malarial kinase, Plasmodium falciparum protein kinase 7 (PfPK7). Partial least square (PLS) methodology coupled with various feature selection methods, viz. stepwise (SW), genetic algorithm (GA) and simulated annealing, was applied to derive QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The statistically significant best 2D-QSAR model having correlation coefficient r 2 = 0.9190 and cross-validated squared correlation coefficient q 2 = 0.8575 with external predictive ability of pred_r 2 = 0.7212 was developed by SW-PLS with the descriptors like StNE-index, T_N_O_2, T_N_O_7, YcompDipole and SaasCE-index. Molecular field analysis was used to construct the best 3D-QSAR model using GA-PLS method, showing good correlative and predictive capabilities in terms of q 2 = 0.7494 and pred_r 2 = 0.8841. The information rendered by 2D- and 3D-QSAR models may lead to a better understanding of structural requirements of PfPK7 inhibitors and also aid in designing novel potent antimalarial molecules.

A Structure-Activity Relationship Study of Imidazole-5-Carboxylic Acid Derivatives as Angiotensin II Receptor Antagonists Combining 2D and 3D QSAR Methods.

Two-dimensional (2D) and three-dimensional (3D) quantitative structure–activity relationship (QSAR) studies were performed for correlating the chemical composition of imidazole-5-carboxylic acid analogs and their angiotensin II

2,4-Dihydropyrano[2,3-c]pyrazole: Discovery of new lead as through pharmacophore modelling, atom-based 3D-QSAR, virtual screening and docking strategies for improved anti-HIV-1 chemotherapy

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Molecular Modelling Studies for the Discovery of New Substituted Pyridines Derivatives with Angiotensin II AT1 Receptor Antagonists

AT1 receptor antagonist activity using partial least squares and k-nearest neighbor, respectively. For comparing the three different feature selection methods of 2D-QSAR, k-nearest neighbor models were used in conjunction with simulated annealing (SA), genetic algorithm and stepwise coupled with partial least square (PLS) showed variation in biological activity. The statistically significant best 2D-QSAR model having good predictive ability with statistical values of

Prospective QSAR-based prediction models with pharmacophore studies of oxadiazole-substituted α-isopropoxy phenylpropanoic acids on with dual activators of PPARα and PPARγ

r^{2} = 0.8040