Novel 1,2,3-triazole derivatives containing benzoxazinone scaffold: Synthesis, docking study, DFT analysis and biological evaluation

• A novel series of benzoxazinone featuring 1,2,3–triazoles have been achieved. • The structural characterization was performed using experimental and theoretical methods. • Compound 8k is selectively antimicrobial potency against S. aureus, and S. pneumoniae . • Compounds 8h and 8k showed better antiproliferative activity compared to DXN. • Docking on cytochrome P4502A13 enzymatic interactions mainly agree with the experimental results. • Compound 8e recorded the lowest energy gap indicating its good chemical reactivity, in agreement with its strong anticancer activity. In order to address the drastic demand for novel broad-spectrum antibacterial and anticancer medicines with enhanced activity, computer modelling was utilized to rationally develop newer anticancer triazole based drugs. A unique series of benzo[d][1,3]oxazin-4-one linked 1,2,3-triazoles was synthesised in five steps, with good yields and an assessment of their antibacterial and anticancer activities. IR spectroscopy, 1 H NMR, 13 C NMR, and mass spectrometry were used to characterize the synthesis of triazole compounds. From antibacterial screening, the prepared derivatives namely, 8a, 8e, 8h and 8k showed excellent inhibitory potential against S. aureus with ZI of 28 ± 0.48, 30 ± 0.42, 30 ± 0.11, 35 ± 0.23 mm respectively, compared to moxifloxacin (33 ± 0.15 mm). Compared to doxorubicin (IC 50 = 2.45 ± 0.14 μM), compounds 8h and 8k demonstrated superior and exceptional cytotoxicity against the A549 cell line (IC 50 = 2.30 ± 0.26 and 1.90 ± 0.30 μM, respectively). Latter All the derivatives were further subjected to in silico docking studies against human lung (PDB: 2P85), VEGFR2 kinase domain (PDB: 3CP9) and could serve as ideal leads for additional modification in the field of anticancer research. Based on docking results, 8e showed that the amino acids Arg 373 (A), Gly 113 (A), Glu 103 (A), Asp 108 (A), Ser 119 (A), Asn 375 (A), Val 374 (A), Lys 387 (A), and Asn 120 (A) exhibited highly stable binding to cytochrome P4502A13 receptor of lung cancer. Furthermore, Density Functional Theory (DFT) calculations are performed to support the molecular docking studies. Compounds 8e, 8h, and 8k were discovered to have estimated energy gaps (eV) of 3.181, 4.034, and 3.539 eV, respectively. Triazole 8h exhibited the lowest chemical hardness (1.962 eV) and the highest chemical softness (0.252 eV), which also suggests that it is more reactive than all the other compounds under study. Moreover, these scaffolds physicochemical characteristics, filtration molecular properties, assessment of toxicity, and bioactivity scores were assessed in relation to ADME (absorption, distribution, metabolism, and excretion). In conclusion, we discovered a novel benzoxazinone linked 1,2,3-triazoles with promising antimicrobial and anticancer activity and a favorable pharmacokinetic profile.