Design, Synthesis, and Anti-Breast Cancer Potential of Imidazole–Pyridine Hybrid Molecules In Vitro and Ehrlich Ascites Carcinoma Growth Inhibitory Activity Assessment In Vivo

Abstract

Breast cancer remains a challenging medical issue and is a high priority for biomedical research despite significant advancements in cancer research and therapy. The current study aims to determine the anticancer activity of a group of imidazole−pyridine-based scaffolds against a variety of breast cancer cell lines differing in their receptor expression (estrogen receptor (ER), progesterone receptor (PR), and HER-2). A series of 10 molecules (coded 5a−5j) were synthesized through multicomponent and alkylation reactions. FTIR, MS, 1 H, and 13 C NMR spectral analyses confirmed the structures and purity of the synthesized molecules. Subsequently, these molecules were tested for their ability to inhibit the viability of cell lines representing carcinoma of the breast, viz., MDA-MB-468 (ER−, PR−, and HER−), BT-474 (ER+, PR+, and HER+), T-47D (ER+, PR+, and HER−), and MCF-7 (ER+, PR+, and HER−) in vitro. Among these 10 molecules, 5a, 5c, 5d, and 5e exhibited better potency, as evidenced by IC 50 < 50 μM at 24 h of treatment against BT-474 and MDA-MB-468 cell lines. However, except for 5d, the IC 50 value is much higher than 50 μM when tested against T47D and MCF-7 cell lines at 24h. Extended treatment for 48 h reduced the effect of these molecules, as an increase in IC 50 was observed. In mice, intraperitoneal administration of 5e retarded the Ehrlich ascites carcinoma (EAC) growth without causing any organ toxicity at the doses tested. In summary, we report the synthesis scheme and key structural requirements for a new series of imidazole−pyridine molecules for in vitro inhibition of the feasibility of breast cancer cells and in vivo inhibition of EAC tumors.

Exploration of N‐Tetra‐Substituted Imidazoles as Effective Agents To Counteract Gastric Cancer Cell Viability: Synthesis and Biological Evaluation

“…The 1,2,4,5‐tetrasubstituted imidazole scaffold consisted of N ‐methyl pyrrole unit at the second position, while the fourth and fifth positions were occupied by phenyl rings. The first position of the imidazole featured different functionalities, thereby influencing the electronic effects on the imidazole‐pyrrole scaffolds [20–21] …”

“…The first position of the imidazole featured different functionalities, thereby influencing the electronic effects on the imidazole-pyrrole scaffolds. [20][21] The synthesis of 2,4,5-trisubstituted imidazole was achieved through a one-pot synthesis, as depicted in Scheme 1. Benzil (1,2-diphenylethane-1,2-dione), N-methyl pyrrole-2-carboxaldehyde, ammonium acetate, and a catalytic amount of iodine were dissolved in ethanol.…”

Development of Novel Pyridine and Pyrimidine Clubbed Bisindoles as Inhibitors of AKT Pathway

“…Another report was made on thiamine hydrochloride catalysed reaction between aldehyde and amines in presence of sodium borohydrate [32] . Similarly, ZnCl2, I2 and KI were reported as a catalyst in various reports on synthesizing new heterocycles [33–36] …”

“…[32] Similarly, ZnCl2, I2 and KI were reported as a catalyst in various reports on synthesizing new heterocycles. [33][34][35][36] In present work, we have synthesized bisindoles containing pyridine and pyrimidine derivatives incorporating green synthesis using thiamine hydrochloride as catalyst and water as solvent. Derivatives 5 a, 5 c, 5 d, 5 e, 5 f and 5 g are most potent having an IC 50 values of 2.48 � 0.39, 1.35 � 0.13, 3.36 � 0.53, 4.05 � 0.61, 1.91 � 0.28 and 8.12 � 0.91 μM respectively, against MCF-7 cells.…”

Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure–Activity Relationships

“…A literature survey reported the importance and usefulness of this scaffold against cancer [ 109 ]. A number of molecules have been developed based on pyridine in the past decades, with potential anti-breast cancer activities [ 110 , 111 , 112 ]. Inspired by the coumarin and pyridine hybridization approach, Fayed et al designed and synthesized a series of coumarin derivatives, and their anticancer activity was tested on various cell lines.…”