Anticancer Evaluation of Novel Quinazolinone Acetamides: Synthesis and Characterization

Abstract

Background: According to the global cancer report of 2019, the burden of cancer will exceed more than 18 million becoming one of the major causes of global mortality rate. There is a pressing need to establish novel drug candidates for cancer treatment, though many anticancer agents are available in the market owing to their adverse effects. In recent years, quinazoline and its derivatives have been considered as a novel class of cancer chemotherapeutic agents that show promising activity against different tumors. Objective: The objective of this study is to evaluate the anti-cancer potential of the novel class of quinazoline tethered acetamide derivatives against six different cancer cell lines. Method: A novel series of various substituted quinazolinone acetamides were synthesized through a feasible scheme. The synthetic scheme involves the conversion of benzoxazinone (from anthranilic acid and benzoyl chloride) intermediate to 3-amino quinazoline-4-one which is further converted to the final amide by tethering with the propionyl chloride employing Schotten-Baumann Reaction conditions. All the synthesized derivatives characterized by IR, 1HNMR and MASS spectral methods and anti-cancer activity evaluated by employing MTT assay for six cancer cell lines and one normal human cell line. Results: All the synthesized compounds were screened for anti-cancer activity against six cancer cell lines, including A 549 (lung), DU 145 (prostate), HT 29 (colon), MCF-7 (breast), SiHA (cervical), B16F10 (mouse skin melanoma) and one normal human fibroblast cell lines. All the compounds displayed a decent cytotoxicity profile when compared with the standard drug, doxorubicin. Among the synthesized compounds (5a to 5n) tested, two compounds, 5f and 5g have demonstrated excellent cytotoxicity against SiHA and MCF-7 cancer cell lines. Conclusion: Comparatively, most of the compounds displayed decent cytotoxicity potential relative to the standard drug, doxorubicin. Further investigations are needed to establish the detailed mechanism of action of the developed novel quinazolinone acetamides.

Recent advances and prospects in the organocatalytic synthesis of quinazolinones

“…Quinazolinone and its derivatives are an essential heterocyclic skeleton that serves a prominent role in several cellular processes and have been established for their remarkable therapeutic significance as antihypertensive, antimicrobial, antihyperlipidemic, anti-inflammatory, and anticonvulsant activities ( Mhaske and Argade, 2006 ; Khan et al, 2016 ). At the same time, some of their derivatives are also used as antitumor chemotherapeutic agents ( Hekal and Abu El-Azm, 2018 ; Hakim et al, 2022 ). For instance, some representative examples of therapeutically potential quinazolinone derivatives are described in Figure 1 .…”

Design, Synthesis and Molecular Docking of Novel Quinazolinone Hydrazide Derivatives as EGFR Inhibitors

“…Because of its broad bio‐activity and structural diversity, it has become an essential functional framework for drug development [12–13] . It has anti‐tumor, anti‐tuberculosis, antibacterial and anti‐HIV‐1 activities [14–17] . It has been found that quinazolinone derivatives can inhibit the phosphorylation of EGFR and regulate the signal pathway of tumor cells, thus producing anti‐tumor cell proliferation [18] .…”