New molecular hybrids of spirochromanone and carbamide: Design, synthesis, docking and in vitro anticancer studies

Among the array of heterocyclic compounds with biological importance, spirochromanone has proven to be a potential pharmacophore embedded in many drug molecules. Herein, we report the design and synthesis of a series of novel molecular hybrids of carbamide and spirochromanone using a convenient three-step synthesis with good yields. All derivatives were screened for their cytotoxic activity using in vitro methods against cancer and non-cancerous cell lines, such as A549, HCT116, U2OS, Jurkat, CCRF-CEM, MOLT-4, RAMOS, K562, MRC-5 and BJ. Among all the screened compounds, C-06-2 was found to be more potent against MOLT-4 with an inhibition value of 45.57 ± 7.56 μM. Additionally, the C-06 series exhibited effective cytotoxicity against Jurkat and CCRF-CEM cell lines with an inhibition value of 23.18±4.20 to 41.43±7.18 μM. Among the twelve compounds, C-05-2, C-06-2 have the best docking scores of -9.3 and −8.8 Kcal/mol, respectively against ITK. The C-06 series showed more than -10 Kcal/mol dock score against BTK. The design and synthesis of a series of new molecular hybrids of carbamide and spirochromanone using a convenient three-step synthesis with good yields. • Designed hybrid molecules were synthesized successfully in a convenient three-step schematic path. • All six series of compounds, including C-04-3 and C-05-2, have shown good cytotoxic action against the RAMOS cell line (BTK). • The compound series six is only cytotoxic to the Jurkat and CCRFCEM cell lines. • RAMOS cell lines exhibited good to moderate activity; • Presented strong evidence of the potent anticancer activities of six series. • Based on our in silico and in vitro findings, it can be concluded that the newly synthesized molecular hybrids of carbamide and spirochromanone derivatives have shown a greater ability to induce anticancer activity.