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ABSTRACT:
The 3-hydroxy-1-benzofuran-2-carbohydrazide was synthesized from 2-hydroxyacetophenone. To deduce the antibacterial and anticancer activity of the 3-hydroxy-1-benzofuran-2-carbohydrazide, it is docked with different biomarkers of cancer cell and bacteria. Grid was generated for each oncoproteins by specifying the active site amino acids. The binding model of best scoring analogue with each protein was assessed from their G-scores and disclosed by docking analysis using the XP visualizer tool. An analysis of the receptor-ligand interaction studies revealed that 3-hydroxy-1-benzofuran-2-carbohydrazide is most active against 3FDN (threonine protein kinase 6) and 3LAU (Arora 2 kinase) biomarkers and have the features to prove themselves as anti-tuberculosis drugs. The Cramer rules of toxicity predicts the toxicological hazard (when administered orally) from the molecular structure. It shows that it is class III toxic compound. The anti-TB studies show that it shows strong activity (1.6 μg/ml) against mycobacterium tuberculosis (H37 RV strain).
KEYWORDS: Benzofurans, Molecular docking, SAR study, 3LAU, Hydrazones, TB-activity.
INTRODUCTION:
Most of the benzofuran compounds [1,2] frequently occur in natural products and are good chelating agents. The compound amiodarone hydrochloride used as an ideal antiarrhythmic drug [3] contains a 2, 3-substituted benzofuran moiety. The synthesis of ester of 1- benzofuran-2-carboxylate derivatives was reported by number of scientists. They can be synthesized by direct condensation of 2-hydroxybenzophenones with ethyl 2- bromoacetate in dry toluene in the presence of sodium hydride, sodium ethoxide in refluxing absolute ethanol [4].
4-Hydroxy benzofuran-6-carboxhydrazide has been synthesized from furfuraldehyde and dimethyl succinate via series of reaction [5]. 5-Chlorobenzofuran-2-carbohydrazide [6] were synthesized from ethyl 5-Chlorobenzofuran- 2-caboxylate and condensed with various substituted aromatic aldehyde to give Schiff base. 5- Bromosalicylaldehyde was treated with hydroxylamine hydrochloride in N,N-dimethyl formamide under reflux conditions forming 5-bromo salicylonitrile which is further treated with ethyl chloroacetate in anhydrous acetone in presence of anhydrous potassium carbonate forming its ethyl ester. The crude ester was treated with potassium carbonate in DMF under reflux condition forming ethyl 5-bromo-3-amino-1-benzofuran-2- carboxylate [7]. Molecular modeling can accelerate and guide to the chemist or scientist for drug design and contribute to the understanding of the biochemical functions of gene products. These molecular modeling techniques used for the study of organic/inorganic/bio molecules use theoretical and computationally based methods to model or mimic the behavior of molecule/s and have been widely applied...