Exploration of imidazole and imidazopyridine dimers as anticancer agents: Design, synthesis, and structure-activity relationship study.

Abstract

Dimerization of proteins/receptors plays a critical role in various cellular processes, including cell proliferation and differentiation. Therefore, targeting such dimeric proteins/receptors by dimeric small molecules could be a potential therapeutic approach to treating various diseases, including inflammation-associated diseases like cancer. A novel series of bis-imidazoles (13-18) and bis-imidazo[1,2-a]pyridines (19-28) were designed and synthesized from Schiff base dimers (1-12) for their anticancer activities. All the synthesized compounds were screened for anticancer activities against three cancer cell lines, including cervical (HeLa), breast (MDA-MB-231), and renal cancer (ACHN). From structure-activity relationship studies, imidazo[1,2-a]pyridines (19-28) showed remarkable cytotoxic activities, with compounds 19 and 24 showing the best inhibitory activities against all three cell lines. Especially, both 19 and 24 were very effective against the breast cancer cell line (19, GI50  = 0.43 µM; 24, GI50  = 0.3 µM), exceeding the activity of the control adriamycin (GI50  = 0.51 µM). The in vivo anticancer activity results of compounds 19 and 24 were comparable with those of the animals treated with the standard drug tamoxifen. Therefore, the dimeric imidazo[1,2-a]pyridine scaffold could serve as a potential lead for the development of novel anticancer agents.

• Authors: Sangeetha Meenakshisundaram, Manoj Manickam, Thanigaimalai Pillaiyar
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 352 Issue 12 Pg. e1900011 (Dec 2019) ISSN: 1521-4184 [Electronic] Germany
• PMID: 31596021 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Archiv der Pharmazie published by Wiley-VCH Verlag GmbH & Co. KGaA on behalf of Deutsche Pharmazeutische Gesellschaft.

Chemical References

• Antineoplastic Agents
• Imidazoles
• Pyridines
• imidazopyridine
• imidazole

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Design
• Humans
• Imidazoles (chemical synthesis, chemistry, pharmacology)
• Mammary Neoplasms, Experimental (drug therapy)
• Molecular Structure
• Protein Multimerization (drug effects)
• Pyridines (chemical synthesis, chemistry, pharmacology)
• Rats
• Structure-Activity Relationship
• Treatment Outcome