Synthesis of new quinazoline-linked fused imidazole-oxazole conjugates; evaluation of anticancer activity, molecular docking, DFT and ADMET studies

A novel series of quinazoline-linked fused imidazole-oxazole conjugates ( 9a-n ) were synthesized and evaluated for their anticancer activity against two breast cancer cell lines such as MDA-MB231 and MCF-7 using the MTT assay. The erlotinib used as a standard reference drug. The anticancer activity outcomes shown that compound 9 l with IC 50 values of 18.20 ± 1.20 μM (MCF-7) and 21.13 ± 1.13 μM (MDA-MB231). Also, compounds 9i , 9j , and 9 k , displayed slightly lower activity, with IC 50 values ranging from 23.10 ± 1.32 μM to 34.02 ± 0.06 μM. Additionally, inhibition assays targeting the tyrosine kinase EGFR showed that compounds 9i , 9j , and 9 l exhibited the greatest EGFR tyrosine kinase inhibitory potency, with IC 50 values of 2.80 μM, 2.93 μM, and 2.20 μM, respectively. Biologically potent compounds showed stronger binding than erlotinib, with docking scores of −8.73 to −8.99 kcal/mol compared to −8.11 kcal/mol. Compound 9i , forming dual hinge hydrogen bonds, was more active than erlotinib, while 9 l achieved the best docking score due to strong hydrophobic interactions. DFT results confirmed higher dipole moments and favourable electronic features, supporting their anticancer potential. SWISS, ADME, and pkCSM were used to evaluate the pharmacokinetics of the potent compounds 9i , 9j , 9 k and 9 l . The four compounds ( 9i , 9j , 9 k and 9 l ) closely fitted all four requirements, except Ghose rule. The quinazoline-linked fused imidazole-oxazole conjugates ( 9a-n ) were synthesized and evaluated for their anticancer activity against two breast cancer cell lines such as MDA-MB231 and MCF-7 using the MTT assay. The anticancer activity outcomes shown that compound 9 l with IC 50 values of 18.20 ± 1.20 μM (MCF-7) and 21.13 ± 1.13 μM (MDA-MB231). Also, compounds 9i , 9j , and 9 k , displayed slightly lower activity, with IC 50 values ranging from 23.10 ± 1.32 μM to 34.02 ± 0.06 μM. Additionally, inhibition assays targeting the tyrosine kinase EGFR showed that compounds 9i , 9j , and 9l exhibited the greatest EGFR tyrosine kinase inhibitory potency, with IC 50 values of 2.80 μM, 2.93 μM, and 2.20 μM, respectively. Biologically potent compounds showed stronger binding than erlotinib, with docking scores of −8.73 to −8.99 kcal/mol compared to −8.11 kcal/mol. Compound 9i , forming dual hinge hydrogen bonds, was more active than erlotinib, while 9l achieved the best docking score due to strong hydrophobic interactions. DFT results confirmed higher dipole moments and favourable electronic features, supporting their anticancer potential. SWISS, ADME, and pkCSM were used to evaluate the pharmacokinetics of the potent compounds 9i , 9j , 9k and 9l . The four compounds ( 9i , 9j , 9k and 9l ) closely fitted all four requirements, except Ghose rule. • Synthesis of quinazoline linked fused imidazole-oxazole conjugates through multi-step synthesis. • Novel quinazoline linked fused imidazole-oxazole conjugates exhibited anti-cancer activity on two breast cancer cell lines, MDA-MB231 and MCF-7. • Biologically potent compounds showed stronger binding than erlotinib, with docking scores of −8.73 to −8.99 kcal/mol compared to −8.11 kcal/mol. • DFT results confirmed higher dipole moments and favourable electronic features, supporting their anticancer potential. • SWISS, ADME, and pkCSM were used to evaluate the pharmacokinetics of the potent compounds 9i , 9j , 9 k and 9 l . The four compounds ( 9i , 9j , 9 k and 9 l ) closely fitted all four requirements, except Ghose rule.