SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF SOME NEW 1,2,4-TRIAZOLO QUINAZOLINE DERIVATIVES

Hamada Abulkhair

doi:10.21608/ajps.2021.187755

Abstract

Cancer is a major public health problem in all countries and remains as one of the top leading causes of death worldwide. Herein we report the synthesis of novel series of triazoloquinazolines as potential anticancer agents. Structures of this set of compounds were confirmed by different spectral data including IR, 1H NMR, 13C NMR, Mass spectra, and elemental analyses. All the newly synthesized compounds were evaluated for their anti-proliferative activity against four human cancer cell lines namely; Hepatocellular carcinoma (HePG-2), Mammary gland breast cancer (MCF-7), Human prostate cancer (PC3) and Colorectal carcinoma (HCT-116)). Results of cytotoxicity evaluation showed that the synthesized compounds displayed moderate cytotoxic activity against the selected cancer cell lines. Compound 9 showed the highest anti-proliferative effect followed by compound 7 against colorectal carcinoma cell line (HCT-116) with IC50 values of 17.35 and 27.05 µM respectively. As well, both compounds showed moderate activity against hepatocellular carcinoma (HePG2) with IC50 values of 29.47 and 39.41 µM respectively.

Highlights

Quinazoline derivatives are biologically important heterocycles and are known to possess a variety of biological activities such as antitumor (Fedorov et al 2014), antimicrobial (Sun et al 2011; Sun, Wei, et al 2010), anti-inflammatory (Sun, Hu, et al 2010), antihistaminic (Awadallah, El-Eraky, and Saleh 2012), antidepressant (Olmo et al 2006), anticonvulsant (Abulkhair et al 2016) and antihypertensive (Holló et al 2014)
Chemistry: The general route for the synthesis of starting triazoloquinazolines is presented in Scheme 1
Anticancer evaluation: Anticancer activities of the synthesized compounds were assessed on four cancer cell lines namely; hepatocellular carcinoma (HePG-2), mammary gland breast cancer (MCF-7), human prostate cancer (PC3) and colorectal carcinoma (HCT-116) using MTT assay (Mosmann 1983)

Summary

Introduction

Quinazoline derivatives are biologically important heterocycles and are known to possess a variety of biological activities such as antitumor (Fedorov et al 2014), antimicrobial (Sun et al 2011; Sun, Wei, et al 2010), anti-inflammatory (Sun, Hu, et al 2010), antihistaminic (Awadallah, El-Eraky, and Saleh 2012), antidepressant (Olmo et al 2006), anticonvulsant (Abulkhair et al 2016) and antihypertensive (Holló et al 2014). All the synthesized compounds were evaluated for their in vitro anticancer activity against four cancer cell lines namely; hepatocellular carcinoma (HePG-2), mammary gland breast cancer (MCF-7), human prostate cancer (PC3) and colorectal carcinoma (HCT-116). Compound 4 was heated in water bath with acetic anhydride (40 mL) for 3-4 hours leaved to cool to obtain 3methyl[1,2,4]triazolo[4,3-c]quinazolin-5(6H)-one (5) in a reasonable good yield.

Results

Conclusion