Design, Synthesis, Anti-Microbial Evaluation, and Docking Studies of New N-Benzyl-3-Indole Derivatives

Sediek, Ashraf A.; Shaddy, Abeer A.; Radwan, Mohamed A. A.; Abdel-aziz, Mohamed S.

doi:10.21608/ejchem.2024.304683.10030

Design, Synthesis, Anti-Microbial Evaluation, and Docking Studies of New N-Benzyl-3-Indole Derivatives

Document Type : Original Article

Authors

¹ Chemical Industries Research Institute, National Research Centre, Dokki, Giza 12622, Egypt.

² Applied Organic Chemistry Department, National Research Centre, Dokki 12622, Egypt.

³ Microbial Chemistry Department, Biotechnology Research Institute, National Research Centre, Dokki, Egypt.

10.21608/ejchem.2024.304683.10030

Abstract

New 3-hydrazinecarbothioamide-N-benzylindol derivatives 3a/b have been synthesized by the reaction of N-benzyl-3-acetylindol 1 with hydrazinecarbothioamide 2a/b. Then compounds 3a/b were cyclized with different α-halocarbonyl derivatives to produce thiazolidinone and thiazole compounds in moderate to excellent yields. The anti-microbial activities were screened for all the newly synthesized compounds. The experimental results indicated that only hydrazinecarbothioamides 3a,b showed good anti-microbial activities toward all the studied microbes compared with the used references. Despite that, compound 12e had anti-bacterial efficacy versus E. coli, compound 12d had anti-microbial activity against C. albicans, and compounds 12c and 12d had anti-fungal action against A. niger. Also, compounds 3a and 3b exhibited higher MIC values than ciprofloxacin. A molecular docking study was conducted for the most potent compounds 3a/b to assess theoretically the anti-microbial effect on the crystal structures of S. aureus and E. coli DNA gyrase B enzymes. The results of molecular docking proved that hydrazinecarbothioamides 3a,b had good binding energy and good binding mode actions towards the DNA gyrase B enzymes through their action with the main amino acids of the aimed enzymes in a similar way to the native inhibitor, consequently preventing cell division that leads to the death of bacteria.

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