Environmentally friendly and efficient TBHP-mediated catalytic reaction for the synthesis of substituted benzimidazole-2-ones: In-silico approach to pharmaceutical applications

• Published in: Environmental research 2024-07, Vol.252, p.118760-118760, Article 118760
• Main Authors: Indira, Meeniga, Surendranath Reddy, E.C., Kamala Prasad, Vasikarla, Satyanarayana Swamy, Vyshnava, Kakarla, Raghava Reddy, Venkata Krishna Reddy, Motakatla, Attiri, Pankaj, Vasu Govardhana Reddy, Peddiahgari, Aminabhavi, Tejraj M.
• Format: Article
• Language: English
• Subjects: ambient temperature; Benzimidazole-2-ones; catalytic activity; computer simulation; Green chemistry; heat shock proteins; hepatoma; hydrogen peroxide; In-silico modelling; ligands; mitochondria; molecular dynamics; oxidation; Pharmaceutical compounds; potassium; Tertiary butyl hydroperoxide; tetrahydrofuran
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1016/j.envres.2024.118760

A novel method was used to synthesize benzimidazole-2-ones from the corresponding benzimidazolium salts. These salts were subsequently reacted with potassium tertiary butoxide (KOtBu), followed by oxidation using tertiary butyl hydrogen peroxide (TBHP) at room temperature in tetrahydrofuran (THF) to obtain the desired products in 1 h with excellent yields. After optimizing the reaction conditions, the study focused on preparing benzimidazole-2-ones with diverse substituents at N1 and N3 positions, including benzyl, 2′,4′,6′-trimethyl benzyl groups, and long-chain aliphatic substituents (hexyl, octyl, decyl, and dodecyl). The compounds were characterized by 1H and 13C NMR spectra, of which compound 2a is supported by single crystal XRD. Benzimidazole-2-one compounds exhibited promising anti-inflammatory and anti-cancer properties. The inhibition of mitochondrial Heat Shock Protein 60 (HSP60) of title compounds was also explored. Computational simulations were employed to assess anti-cancer properties of 19 benzimidazole-2-one derivatives (potential drugs). In-silico docking studies demonstrated promising binding interactions with HSP60, and these results were supported by molecular dynamics simulations. Notably, molecules 2b and 2d exhibited high affinity for HSP60 protein, highlighting their potential efficacy. The developed ligands were viable for the treatment of hepatocellular carcinoma (HCC). The findings provide valuable initial evidence supporting the efficacy of benzimidazole-2-ones as HSP60 inhibitors and lay the foundation for subsequent studies, including in-vitro assays. [Display omitted] •In this study, the benzimidazole-2-ones are synthesized from the salts and oxidant.•This study dramatically improved catalytic efficacy and cost-effective production.•The novel approach offered a greener path with a lower ecological footprint.•Molecular Docking enables anticipatory results for cancer targets.•The molecules developed may offer novel avenues for drug development.