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.
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