Design and syntheses of 7-nitro-2-aryl-4 H-benzo[ d][1,3]oxazin-4-ones as potent anticancer and antioxidant agents

Ayesha Bari; Zulfiqar Ali Khan; Sohail Anjum Shahzad; Syed Ali Raza Naqvi; Shakeel Ahmad Khan; Hira Amjad; Ahsan Iqbal; Muhammad Yar

doi:10.1016/j.molstruc.2020.128252

Design and syntheses of 7-nitro-2-aryl-4 H-benzo[ d][1,3]oxazin-4-ones as potent anticancer and antioxidant agents

J Mol Struct. 2020 Aug 15:1214:128252. doi: 10.1016/j.molstruc.2020.128252. Epub 2020 Apr 13.

Authors

Ayesha Bari¹, Zulfiqar Ali Khan¹, Sohail Anjum Shahzad², Syed Ali Raza Naqvi¹, Shakeel Ahmad Khan³, Hira Amjad⁴, Ahsan Iqbal¹, Muhammad Yar⁵

Affiliations

¹ Department of Chemistry, Government College University, Faisalabad, 38000, Pakistan.
² Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan.
³ Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, China.
⁴ Department of Chemistry, Government College University, Lahore, 54000, Pakistan.
⁵ Interdisciplinary Research Center in Biomedical Materials, COMSATS University Islamabad, Lahore Campus, Lahore, 54000, Pakistan.

Abstract

A group of new nitro substituted benzoxazinones (3a-k) were synthesized from easily available 4-nitroanthranilic acid. All the synthesized compounds were characterized by FT-IR, ¹H NMR, ¹³C NMR, mass spectrometry and elemental analysis. Anti-proliferative and pro-apoptotic potential of all the synthesized compounds (3a-k) was evaluated by MTT and Hoechst 33258 staining assay respectively whereas their antioxidant properties were determined via DPPH free radical scavenging assay. The most active compounds (3a, 3c and 3k) showed significant cytotoxic potential against HeLa cells with an inhibition of cell viability that ranged between 28.54 and 44.67% (P < 0.001). Albeit statistically different, the anti-proliferative effect of 3c was in close match with that of the reference drug doxorubicin. Likewise, the test compounds showed profound pro-apoptotic potential with an apoptotic index that ranged between 52.86 and 75.61%. Besides, the docking studies revealed a higher efficiency for compounds (3a and 3h) owing to their better affinity and inhibition constant (K_i = 4.397 and 3.713 nmol) respectively. The antioxidant potential of synthesized benzoxazinones (3a-k) was in close agreement with the experimental anticancer results with a percent inhibition from 34.45 to 85.93% as compared to standard (90.56%).

Keywords: Benzoxazin-4-ones; DPPH free radical scavenging assay; Human cervical carcinoma.