Evaluation of Inhibitory Effect and Docking Study of Triazolyl Chromanone Oxime Ether Derivatives on Aromatase Enzyme Effective in Breast Cancer



Hariri R¹ ; Baeeri M² ; Mohammadhosseini N³ ; Emami S⁴ ; Foroumadi A⁵ ; Tehrani MB¹ Show Affiliations
Source: Journal of Mazandaran University of Medical Sciences Published:2023

Abstract

Background and purpose: The spread of cancer, coupled with the challenges posed by complex treatments, stands as one of the foremost medical issues in today's world. Researchers consistently strive to identify novel compounds with enhanced efficacy and reduced side effects. Aromatase, a pivotal enzyme in estrogen receptor-positive breast cancer, plays a significant role. Estrogens, crucial for human physiology, particularly in women, contribute to sexual development and reproduction. The adverse effects associated with specific aromatase inhibitors underscore the imperative to discover new inhibitors characterized by higher selectivity, lower toxicity, and improved potency. Materials and methods: This research is a basic study in which the semi-prepared aromatase kit was used to investigate synthetic compounds, specifically triazolyl chromanone oxime ethers. The most promising compounds were selected and subjected to molecular docking studies based on the inhibition results obtained. Results: Out of the 40 compounds examined, seven samples exhibiting the most pronounced inhibitory effects were chosen for further scrutiny and IC50 determination. Notably, derivatives 6b and 20b demonstrated the most robust inhibitory effects, with IC50 values of 0.37 and 0.69 μM, respectively. Examining the interactions between these compounds and the aromatase enzyme revealed a significant relationship with the enzyme's active site. Conclusion: In conclusion, the evaluation of various derivatives containing the triazolyl chromanone oxime ether structure suggests their considerable potential as aromatase enzyme inhibitors. Further exploration involving the design of structures within this category holds the promise of yielding more effective derivatives for inhibiting this enzyme. © 2023, Mazandaran University of Medical Sciences. All rights reserved.