"SYNTHESIS AND MOLECULAR DOCKING STUDIES OF NOVEL PYRROLYL BENZAIMIDAZOLE DERIVATIVES AS ANTICONVULSANT AGENTS

The various novel pyrrolyl benzamide derivatives were synthesized and molecular docking studies were carried out further few compounds evaluated for anticonvulsant activity against MES and PTZ induced convulsions. Purity of the newly synthesized compounds confirmed by using TLC and structures were confirmed by using IR, NMR, ¹³C and Mass spectra. Appropriate o-phenylene diamine(1) is treated with para amino-2-chloro benzoic acid (2) in ethanol and reaction mixture made alkaline by adding 10% sodium hydroxide solution to form substituted benzimidazole-2-chloro aniline(3a-e) which is further stirred with 4-pyrrole-1-yl-benzoic acid(4) and 4-(2, 5-dimethyl-1yl)-benzoic acid (5) by dissolving in a dry DMF in presence of HBTU and DIEA yielded the corresponding final compounds(6a-e) and (7a-e). and o-phenylene diamine (1) is treated with para-amino benzoic acid (8) in ethanol and reaction made alkaline by adding 10% sodium hydroxide solution to form substituted benzimidazole aniline (9a-e) which is further stirred with4-(2, 5-dimethyl-1yl)-benzoic acid (5) by dissolving in a dry DMF in presence of HBTU and DIEA yielded the corresponding final compounds(10a-e). Docking study was performed by Surflex-Dock program that is interfaced with Sybyl-X 2.0. Compounds 7e and 10d showed excellent consensus scoreat 7.17 & 7.26 respectively. Docking study reveals that all the compounds have showed very good docking score against the enzyme. The few newly synthesized compounds were screened for their anticonvulsant activity. Compounds 10a (9.8+0.34) and 10e (11.83+0.44) showed significantly decrease in hind limb extension against MES induced convulsions. Compound 6e (140+2.02) and 10e (160+2) showed protection against PTZ induced convulsions. Simultaneously activity is compared with control and standard group. The newly synthesized novel series of pyrrolyl benzamide derivatives may be developed into potential class of anticonvulsant agents in future.