A potent therapeutic scaffold fusing quinazolinone/melatonin for future colorectal cancer interventions: design, one-pot synthesis, biological and ADME-tox modeling studies

Abstract Colorectal cancer is one of the most incident and lethal cancers in the world. The search for new compounds to treat this disease is being motivated by the occurrence of side effects and the rising in the resistance to chemotherapy. We synthesized a new class of conjugates bearing quinazolinone and melatonin which were prepared in good yields (63–93%) through one-pot three-component approach. quinazolinone/melatonin conjugates were proved against SW480 human colorectal adenocarcinoma cells and non-malignant colonic cells (NCM460). The cytotoxic and antiproliferative activities were determined through the sulforhodamine B assay. Compounds 1f , 1g and 1i–l displayed the best activity, being hybrids 1i–l the most selective against malignant cells, causing either a cytostatic and/or cytotoxic effect with evident morphological changes. Moreover, a theoretical drug-like/pharmacokinetics/toxicological study suggested that the hit-promising compounds 1i and 1j would have a great chance to advance to further preclinical studies as anti-cancer therapeutic candidate for oral oncological management. Our study evidently identified the potency of these quinazolinone/melatonin hybrids to be a prototype drug for further investigations toward novel therapeutics treatments of colorectal cancer.