Development of Imidazole Pyridine hybrids as multi targeting anticancer agents

Abstract

Cancer is the most lethal condition and cause of mortality in the worldwide, after cardiovascular disease. The development of chemotherapy drugs that focus on the main symptoms was proposed. In clinical studies for a number of disease conditions, many drugs containing imidazoles have been examined for their potential medical use. The explosive growth of imidazole-based medicinal chemistry shows that molecules generated from imidazoles have potential therapeutic benefits for curing fatal diseases. The ring contains electronic-rich properties that make it easier to bind to a variety of proteins, enzymes and receptors when compared to other heterocyclic rings. Chapter 2 introduces a series of fifteen novel imidazole-pyridine-based molecules that have been synthesized and analyzed using a proliferation assay against cell lines of liver ((HepG2, HUH-7, and PLC/PRF/5), lung (H1299) and colon (HCT116) adenocarcinomas. The result demonstrated that compounds 5a, 5d, 5e, and 5f were the most active (IC50lt 50 µM at 24hr of treatment against BT-474 and MDA-MB 468 cell lines. But, except 7d, the IC50 value is much higher than 50 µM when tested against T47D and MCF-7 cell lines at 24hr. Extended treatment for 48h reduced the effect of these molecules as an increase in the IC50 was observed. In mice, intraperitoneal administration of 7e retarded Ehrlich ascites carcinoma (EAC) growth without causing any organ toxicity at the doses tested. In summary, we report here, the synthesis scheme, key structural requirements for a new series of imidazole-pyridine molecules for inhibiting the viability of breast cancer cells in vitro and EAC tumors in vivo. Chapter 4 introduces the library of novel indole fused imidazole compounds were designed and synthesized. All hybrids were tested for their in vitro anticancer activity against various normal cell lines and human cancer cell lines (Vero, 3T3-L1, H9c2, L929, TH-1B1, MCF-7, A549, Caco-2, SKOV-3, A-431, HeLa, HepG2, SK-MEL-2, B16F10, SKNSH and SHSY5Y) by using the standard MTT assay.