Benzimidazole: A Multifacted Nucelus for Anticancer Agents

Abstract

: Cancer is characterized by an uncontrolled proliferation of cells, dedifferentiation, invasiveness and metastasis. Endothelial growth factor (eGF), Insulin-like growth factor (IGF), Platelet derived growth factor (PDGF), Fibroblast growth factor (FGF), Vascular endothelial growth factor (VEGF), Checkpoint kinase 1 & 2 ( Chk1 & Chk2), Aurora kinases, Topoisomerases, Histone deacetylators (HDAC), Poly(ADP-Ribose)polymerase (PARP), Farnesyl transferases, RAS-MAPK pathway and PI3K-Akt-mTOR pathway are some of the prominent mediators implicated in proliferation of tumor cells. A huge artillery of natural and synthetic compounds as anticancer, which act by inhibiting one or more of the enzymes and/or pathways responsible for progression of tumor cells, is reported in literature. The major limitations of anticancer agents used in clinics as well as of those under development in literature are normal cell toxicity and other side effects due to lack of specificity. Hence, medicinal chemists across the globe have been working since decades to develop potent and safe anticancer agents from natural sources as well as from different classes of heterocycles. Benzimidazoles is one of the most important and explored heteronucelus because of its versatility in biological actions as well as synthetic applications in medicinal chemistry. Structural similarity of amino derivatives of benzimidazole with purines makes it a fascinating nucleus for the development of anticancer, antimicrobial and anti-HIV agents. This review article is an attempt to critically analyze various reports on benzimidazoles derivatives acting on different targets to act as anticancer so as to understand the structural requirements around benzimidazole nucleus for each target and enable medicinal chemists in rational development of antitumor agent.

Anti-Angiogenetic and Anti-Lymphangiogenic Effects of a Novel 2-Aminobenzimidazole Derivative, MFB

“…Benzimidazole is thus recognized as a key pharmacophore in the field of drug discovery. In addition to other biological actions and beneficial effects, benzimidazoles also possess potential anti-proliferative and anti-tumor activities ( 53 , 54 ). We noted that the 2-aminobenzimidazole-based compound, MFB, reduced cell viability in SW480 colorectal cancer, A549 lung cancer, B16F10 melanoma and GBM8901 glioma cells.…”

Long-Wavelength Absorbing Benzimidazolo-Chlorin for Enhanced Photodynamic Therapy

“…Benzimidazole, a key component of vitamin B12, is a benzoheterocyclic compound containing two nitrogen atoms. There have been numerous reports of benzimidazole derivatives with anticancer activity. − Furthermore, benzimidazole is an effective chromophore that combines with chlorophyll-a and conjugates with porphyrin rings, increasing electron delocalization and causing a red-shift of the maximum absorption wavelength to synthesize long-wavelength absorbing PS. , …”

Novel 1,2,5-Trisubstituted Benzimidazoles Potentiate Apoptosis by Mitochondrial Dysfunction in Panel of Cancer Cells

“…The literature survey revealed that the benzimidazole derivatives have been extensively investigated as potential anticancer agents, and these benzimidazole derivatives exhibit anticancer effects through different mechanisms of action such as intercalating mode of action (DNA binding), nonintercalating mode of action (topoisomerases inhibition), DNA alkylation (DNA cleavage), acting on enzyme antimetabolites [DihydrofolateReductase (DHFR) inhibition], sirtuin inhibition (SIrt1 and SIrt2 inhibition), acting on structural proteins (tubulin protein inhibition), and protein kinase inhibition. − …”