SYNTHESIS, ANALYSIS ADME-TOX PARAMETERS AND ANTI-CANCER ACTIVITY OF N-(5-R-BENZYLTHIAZOLE-2-YL)-2-MORPHOLIN-4-YL-2-THIOXOACETAMIDES

Abstract

Aim. Study of the synthesis, analysis of ADME-Tox parameters and anti-cancer activity of a series of N-(5-R-benzylthiazole-2-yl)-2-morpholin-4-yl-2-thioxoacetamides. Methods. Organic synthesis, 1H NMR spectroscopy, analytical method, in silico ADME-Tox analysis and in vitro cytotoxicity assay. Results. The series of new N-(5-R-benzylthiazole-2-yl)-2-morpholin-4-yl-2-thioxoacetamides was synthesized according to a convenient synthetic method. Their structures were confirmed by 1H NMR spectroscopy and microanalyses. Using the internet resources of SwissADME and pkCSM-pharmacokinetics, the ADME-Tox profiles of the synthesized compounds were calculated. It was determined that the substances were within the optimal limits of bioavailability. All compounds meet the criteria of drug similarity according to the rules of Lipinski, Weber, Egan and Mugge. It is also determined that low toxicity is predicted for these substances. The synthesized compounds were tested in vitro for their antitumor activity according to the Developmental Therapeutic Program of the National Cancer Institute (NCI) (www.dtp.nci.nih.gov) against 60 cancer lines in the concentration of 10 µM. Human tumor cell lines from nine different cancer types were used: leukemia, melanoma, lung, colon, CNS, ovarian, kidney, prostate and breast cancer. Screening results showed that, in most cases, these compounds are of low activity. An exception is the renal cancer line UO-31, which was moderately sensitive to all synthesized compounds. Conclusions. A series of 2-aminothiazole hybrids containing morpholine moiety was synthesized and studied in silico ADME-Tox profiles. The ADME-Tox profiles indicated good oral bioavailability and low toxicity. Synthesized compounds were tested in vitro for their anti-cancer activity. They showed moderate antiproliferative activity.