Anticancer Evaluation of Novel Quinazolinone Acetamides: Synthesis and Characterization

Author(s):

Farhana Hakim, Roshan Salfi*, Darna Bhikshapathi and Abdullah Khan   Pages 926 - 932 ( 7 )

Abstract:

Background: According to the global cancer report 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. <P> Objective: To evaluate the anti-cancer potential of the novel class of quinazoline tethered acetamide derivatives against six different cancer cell lines. <P> Methods: 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 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 were evaluated by employing MTT assay for six cancer cell lines and one normal human cell line. <P> 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. <P> 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.

Keywords:

Quinazolinone, anti-cancer activity, EGRF-TK, Schotten-Baumann reaction, MTT assay, cell line.

Affiliation:

Research Scholar, Career Point University, Kota, Rajasthan-325003, Research Supervisor, Career Point University, Kota, Rajasthan-325003, TRR College of Pharmacy, Meerpet, Hyderabad- 500097, Telangana, KPJ Healthcare University College, Nilai, Negeri Sembilan Darul Khusus

Graphical Abstract:

Read Full-Text article