IN VITRO ANTIOXIDANT, ANTIMICROBIAL AND ADMET STUDY OF NOVEL FURAN/BENZOFURAN C-2 COUPLED QUINOLINE HYBRIDS

Objectives: Synthesis of novel 2-(benzofuran-2-yl) and 2-(furan-2-yl) quinoline-4- carboxylates and their [2-(1-benzofuran-2-yl) quinolin-4-yl] methanol, [2-(1-furan-2-yl) quinolin-4-yl] methanol and its derivatives for antioxidant, antimicrobial and ADMET study.Methods: Synthesis was carried with conventional method and the structures were confirmed by IR, 1H NMR, 13C NMR and mass spectral analysis. The antioxidant activity was performed by DPPH and H2O2 radical scavenging method. Antimicrobial investigation was established by cup plate and food poison technique. The in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) study of the drug was carried out in ACD/lab-2.Results: The antioxidant activity results revealed that, compounds 4b-c, 5a-b, 10c and 10f exhibited good DPPH radical and hydrogen peroxide scavenging activity. The antibacterial results revealed that, compounds 4c, 5a-b, 10b, 10d and 10f exhibited good activity against Escherichia coli, Klebsiella pneumonia and Salmonella typhimurium. Further, the antifungal activity results showed that, compounds 4c, 5c and 10c-e were showing good activity against Aspergillus flavus and Candida neoformans.  The mean value of P<0.05 were considered to be statistically significant. The ADMET results revealed that compounds emerged as a potential candidate for antioxidant and antimicrobial agents.Conclusion: The study reveals that compounds containing furan/benzofuran coupled heterocycles are play the important role for activity as they possess potent antioxidant and antimicrobial agents. The in silico ADME analysis also suggesting the compounds were in acceptable range to obey the pharmacokinetic parameters.Â

The Electrochemical Behaviour of Novel Multifunctional a-Hydroxymethylated Nitroalkenes at Glassy Carbon and Wax Impregnated Carbon Paste Electrodes

The electrochemical behaviour of novel multifunctional a-hydroxymethylated nitroalkenes was studied with respect to oxidation of –OH moiety and reduction of nitro group using the cyclic voltammetric technique at glassy carbon and wax impregnated carbon paste electrodes with sulphuric acid as the supporting electrolyte. The –OH moiety attached to the nitroalkene side chain was found to undergo irreversible four electrons electrochemical oxidation to form an acid at the glassy carbon electrode but no oxidation was observed at the wax impregnated carbon paste electrode. Oxidation in sulphuric acid medium becomes easier with increasing the sulphuric acid concentration. This unusual behaviour is attributed to the formation of a sixmembered cyclic structure at lower concentrations of sulphuric acid due to intramolecular hydrogen bonding. Going to the lower potential range, reduction of nitro group was observed in sulphuric acid medium both at the glassy carbon and wax impregnated carbon paste electrodes. A comparative study indicated easier reduction at the glassy carbon electrode. Non hydroxymethylated beta nitroalkenes undergo reduction at a lower negative potential compared to the corresponding a-hydroxymethylated nitroalkenes

SYNTHESIS, ANTIPLASMODIAL AND ADMET STUDIES OF 4-METHYLAMINO-2-PHENYLQUINOLINE ANALOGS

Objective: Synthesis, antiplasmodial and absorption, distribution, metabolism, excretion and toxicity (ADMET) studies of 4-methylamino-2-phenylquinoline analogs. Methods: The synthesis of 4-methylamino-2-phenylquinoline analogs 7(a-j) by reacting substituted 4-(chloromethyl)-2-phenylquinoline 6(a-c) with secondary amines to explore their antimalarial property against P. falciparum RKL-2 strain and in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) properties using ACD/I-Lab 2.0. The synthesized structures were confirmed by IR, NMR and Mass spectral analysis.Results: The results revealed that at 100 μg/ml, compounds 7a, 7d and 7i were found to be potent with percentage inhibition of 88.0±1.1, 79.1±1.1, 90.2±0.1, respectively. The compounds 7b, 7e, 7f and 7h were moderately active with 59.9±1.2, 48.5±2.0, 35.2±1.1 and 52.0±0.3 and the remaining compounds 7c, 7g and 7j exhibited mild activity 32.2±1.2, 36.8±3.0 and 28.7±2.0. The absorption, distribution, metabolism, excretion and toxicity (ADMET) studies of title compounds were analyzed and found to be obeying the Lipinski rule of five and are non-toxic.Conclusion: The C4 of quinoline ring with morpholine 7a, piperidine 7d and imidazole 7i substitutions were promising enough to be taken as lead molecules in the drug discovery of new antimalarial. The in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies of the molecules were found to be obeying the Lipinski rule of five good drug likeliness.Â

TOXICITY AND MOLECULAR DOCKING STUDIES OF TETRAHYDROQUINOLINES AGAINST MICROBIAL, CANCER, RETINOIC ACID RECEPTOR, INFLAMMATORY, CHOLESTEROL ESTER TRANSFERASES AND PARASITIC PROTEIN RECEPTORSTOXICITY AND MOLECULAR DOCKING STUDIES OF TETRAHYDROQUINOLINES AG

Objective: Synthesis of 2-methoxy-4-(3-methyl-2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)phenol derivatives (4a-i) and to study their inhibitory effects towards inflammatory, cancer, retinoic acid, cholesterol esterase, parasitic and microbial proteins.Methods: Various 2-methoxy-4-(3-methyl-2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)Phenols (4a-i) were synthesized via imino Diels-Alder reaction and were characterized by IR, 1H NMR, 13C NMR mass spectroscopy and elemental analysis. All 2-methoxy-4-(3-methyl-2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)Phenols (4a-i) and six FDA approved reference drugs were docked against inflammatory, cancer, retinoic acid, cholesterol esterase, parasitic and microbial protein receptors. The results were studied and validated based on molecular docking analysis.Results: The compounds 4a-i were less toxic on internal tissues and show no side effect. The compounds 4c and 4f were strongly interacts with active site amino acids Arg210, His107, Ala197, Thr198 and Arg195 of binding energy -16.0728 kcal/mol and -56.5169 kcal/mol with inflammatory protein. The compound 4b and 4f binds with cancer protein shows -8.99845 and -5.70191 kcal/mol of energy exhibits significant anticancer properties. The compound 4a shows 7 hydrogen bonds with retinoic acid protein within amino acids Asn1185 and Arg1309 with energy of -47.423 kcal/mol than remaining compounds. The compound 4g shows 5 hydrogen bonds of energy -32.9844 kcal/mol with amino acids Arg155, Gln124, Leu122 with microbial protein. The compounds 4c, 4d and 4i exhibits 3 hydrogen bonds within active site amino acids of energy -8.29829 kcal/mol, against cholesterol esterase protein. Nevertheless, all 4a-i compounds shows strong interaction with parasitic protein.Conclusion: The compounds 4a, 4c, 4f, 4g, and 4h were identified as multifunctional lead compounds hence; these compounds could be considered as potential lead molecules in the future study. Â