A series of six-membered lactam derivatives containing C, O and S atoms in position 4 were synthesized using microwave methodology through coupling reactions. The novel compounds were synthesized following two step reaction to yield fifteen derivatives. The final derivative N-(4-(3-oxotiomorpholin)phenyl) hexanamide was selectively toxic to the HCT-116 cell line over the HeLa cancerous and HEK-293 human non-malignant control cells with low inhibition Factor Xa (FXa) activity. The new products were characterized by spectral data including 1 H and 13 C nuclear magnetic resonance (NMR), infrared (IR) and high-resolution mass spectrometry (HRMS). Cytotoxicity of products on HCT-116, HeLa, HEK-293 cell lines and FXa activity assays are also reported. Keywords: lactam derivatives, microwave, coupling reactions, cytotoxic activity, FXa activity IntroductionAccording to statistics from the World Health Organization (WHO), 1 the mortality rate associated with age-standardized cancer was 115.3 per 100,000 inhabitants in 2012. The analysis reported by the Department of Health Statistics and Information (DEIS), which is a department within the Chilean Health Ministry (MINSAL), reported that colon cancer was the cause of 1,410 deaths. This finding corresponds to a mortality rate of 8.2 per 1,000 people in 2012.2 This epidemiologic data supports the pressing need for on-going research to find novel compounds for the treatment of colon cancer.Indeed, existing data from basic cancer research shows that the haemostatic components and the cancer biology are interlinked in multiple ways.3 Nonetheless, it is noteworthy that while a group of cancer cells is capable of activating the clotting system, haemostatic factors play a role in tumor progression. 4 Moreover, current antineoplastic drugs are useless due to their high toxicity, side effects and low selectivity. Thus, novel scaffolds for the development of antineoplastic drugs has become a rapidly growing field of scientific interest, and highlight the development of small molecules with activity involving lactam moieties. Usually, reported protocols for synthesizing these interesting kinds of structures require multiple-step synthesis, long reaction times and high temperatures which ultimately results in low yields of the desired products. In this context, our research group is focused on the synthesis of new 4-C, 4-O and 4-S lactams with an aromatic amide substituent by means of using microwave assisted methodologies in order to diminish reaction time and increase the yield of the product. In this research, a modified Ullmann type reaction, using microwave approach and peptide coupling methods 7 was performed to provide a new group of interesting compounds with enhanced Microwave Assisted Synthesis of Novel Six-Membered 4-C, 4-O and 4-S Lactams Derivatives J. Braz. Chem. Soc. 204 selective cytotoxic activity for neoplastic cells HCT-116 (human colon cancer).The chemical structure of these newly synthesized molecules has a similar main core of Factor Xa (FXa) commercially av...
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