Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity

Abstract

Two new classes of hybrid quinoline–imidazole/benzimidazole derivatives (the hybrid QIBS salts and QIBC cycloadducts) were designed and synthesized to evaluate their anticancer and antimicrobial activity. The strategy adopted for synthesis is straight and efficient, in four steps: N-acylation, N-alkylation, quaternization and a Huisgen 3 + 2 cycloaddition. The in vitro single-dose anticancer assay of forty six hybrid quinoline-benzimidazole compounds reveal that one QIBS salt (11h), has an excellent quasi nonselective activity against all type of cancer cell with an excellent PGI in the area of 90–100% and very good lethality. Three others quinoline–imidazole/benzimidazole hybrids (8h, 12h, 12f) has an excellent selective activity against some cancer cell lines: breast cancer MDA-MB-468 and Leukemia HL-60 TB). The five-dose assay screening confirms that compound 11h possesses excellent anti-proliferative activity, with GI50 in the range of nano-molar, against some cancer cell lines: Leukemia HL-60 TB, Leukemia K-526, Leukemia RPMI-8226, Breast cancer MDA-MB-468, Lung cancer HOP-92 and Ovarian cancer IGROV1. The antibacterial assay indicates that three hybrid QIBS salts (12f, 12c, 12d) have an excellent activity against Gram-negative bacteria E. coli (superior to control Gentamicin) while against Gram-positive bacteria S. aureus only one compound 8i (R2 = -CF3) exhibits a significant activity (superior to control Gentamicin). The MIC assay indicates that two other compounds (11h, 12h) are biologically active to a very low concentration, in the range of nano-molar. We believe that all these excellent assets related to anticancer and antibacterial activities, make from our hybrid quinoline–imidazole/benzimidazole compounds bearing a phenyl group (R2 = –C6H5) in the para (4)-position of the benzoyl moiety a good candidate for future drug developing.

Hybrid Azine Derivatives: A Useful Approach for Antimicrobial Therapy

“…In continuation of our concern for new compounds with antimicrobial activity, Diaconu et al [ 52 ] synthesized a large library of hybrid imidazole- and benzimidazole-quinoline derivatives and studied their antimicrobial properties. The reaction pathway ( Scheme 42 ) involves an initial N -acylation reaction of 8-aminoquinoline, followed by an N -alkylation of the -NH- amino group from imidazole/benzimidazole heterocycle, when the key imidazole-quinoline 128a , b and benzimidazole-quinoline 129a , b hybrids are obtained.…”

Anti-proliferative activity of nitroquinolone fused acylhydrazones as non-small cell human lung cancer agents

“…[35][36][37] The quinoline core has also proven anti-cancer and anti-microbial activities. 38,39 Several studies have reported anti-cancer activities against diverse cell lines when functionalising this versatile heterocycle with hydrazide substitution. [40][41][42] Introduction of a nitro group at the 8th position on the quinoline ring stabilises the moiety through hydrogen bonding with the ring nitrogen atom.…”

Deciphering the Mechanism of MRSA Targeting Copper(II) Complexes of NN2 Pincer-Type Ligands

“…53 Further, the amide functional group is also an option to increase the antimicrobial activity, as understood from the literature. 55,56 Thus, an amidate-based aminoquinoline group linked with alkyl chains can exhibit enhanced antimicrobial activity.…”

“…In this connection, many of the reported pharmaceutical compounds contain nitrogen-based heterocycles, for example, the quinoline pharmacophore. − More specifically, functionalized quinoline can play a very important role in increasing the therapeutic propensity of the drugs. − Quinoline drugs can induce apoptosis, inhibit the cell cycle, and disrupt cell migration to damage pathogenic cells, and most importantly, they are promising against biofilm-associated infections. , Moreover, the introduction of electron-releasing alkyl chains and biologically active morpholine into the copper complexes can enhance antimicrobial activity. − The SAR studies show that compounds having methyl substitution at one end and electron-withdrawing groups at the other side can increase the electrophilic nature of the compound and thus facilitate the nucleophilic attack over the cellular thiol groups . Further, the amide functional group is also an option to increase the antimicrobial activity, as understood from the literature. , Thus, an amidate-based aminoquinoline group linked with alkyl chains can exhibit enhanced antimicrobial activity.…”