Amino substituted benzimidazo[1,2- a ]quinolines: Antiproliferative potency, 3D QSAR study and DNA binding properties

Abstract

We describe the synthesis, 3D-derived quantitative structure-activity relationship (QSAR), antiproliferative activity and DNA binding properties of a series of 2-amino, 5-amino and 2,5-diamino substituted benzimidazo[1,2-a]quinolines prepared by environmentally friendly uncatalyzed microwave assisted amination. The antiproliferative activities were assessed in vitro against colon, lung and breast carcinoma cell lines; activities ranged from submicromolar to micromolar. The strongest antiproliferative activity was demonstrated by 2-amino-substituted analogues, whereas 5-amino and or 2,5-diamino substituted derivatives resulted in much less activity. Derivatives bearing 4-methyl- or 3,5-dimethyl-1-piperazinyl substituents emerged as the most active. DNA binding properties and the mode of interaction of chosen substituted benzimidazo[1,2-a]quinolines prepared herein were studied using melting temperature studies, a series of spectroscopic studies (UV/Visible, fluorescence, and circular dichroism), and biochemical experiments (topoisomerase I-mediated DNA relaxation and DNase I footprinting experiments). Both compound 36 and its bis-quaternary iodide salt 37 intercalate between adjacent base pairs of the DNA helix while compound 33 presented a very weak topoisomerase I poisoning activity. A 3D-QSAR analysis was performed to identify hydrogen bonding properties, hydrophobicity, molecular flexibility and distribution of hydrophobic regions as these molecular properties had the highest impact on the antiproliferative activity against the three cell lines.

Design, Synthesis, DNA Binding, and Docking Studies of Thiazoles and Thiazole‐Containing Triazoles as Antibacterials

“…Due to the strong stacking interaction between the base pairs of DNA and aromatic chromophores. The DNA binding constants of 4 a‐g and 5 a‐f (Table ) concluded that these compounds interacted with CT‐DNA through intercalation mode which is well supported by the available literature for similar kind of compounds . It is also indicated that the compounds form adducts with DNA through intercalation and were stabilized by hydrophobic and hydrogen bonds interactions ,.…”

Synthesis, Characterization, Antibacterial and Antioxidant Studies of Some Heterocyclic Compounds from Triazole‐Linked Chalcone Derivatives

“…Attributable to the strong stacking interaction between the aromatic chromophores and the base pairs of DNA. The DNA binding constants of 3 f , 4 a , 5 a, 6 a, 7 a , and 8 a (Table ) inferred that these compounds interacted with CT‐DNA through intercalation mode which is well supported by the available literature for similar kind of compounds . It is also suggested that the compounds form adducts with DNA via intercalation and were stabilized by hydrophobic and hydrogen bonds interactions .…”

Benzimidazole Scaffold as Anticancer Agent: Synthetic Approaches and Structure–Activity Relationship

“…Compound 625 showed most potent cytotoxic activity with IC 50 > 50 μM, 39.55 ± 2.28 μM, >50 μM, >50 μM, >50 μM, >50 μM, 41.23 ± 3.82 μM and >50 μM against cancer cell lines using sunitinib as a reference standard. Perin et al reported the anti‐proliferative and DNA binding properties of a series of 2‐amino, 5‐amino and 2,5‐diamino‐substituted benzimidazo[1,2‐a]quinolones and assessed for anti‐proliferative activity against colon, lung and breast carcinoma cell lines (Scheme ). Compounds 630a , b were found to be most potent with IC 50 = 0.6 ± 0.3 μM, 2 ±1 μM, 1 ± 0.8 μM and 0.3 ± 0.08 μM, 0.6 ± 0.2 μM and 0.5 ± 0.04 μM using doxorubicin and etoposide as the standard drugs.…”