Synthesis, Characterization and Exploration of Anticancer Activity of S-methoxy, 5-hydroxy and S,7-dibromoisatin Thiosemicarbazones,

Abstract

SYNTHESIS, CHARACTERIZATION AND EXPLORATION OF ANTICANCER ACTIVITY OF 5-METHOXY, 5-HYDROXY AND 5,7-DIBROMO ISATIN THIOSEMICARBAZONES ABSTRACT Thiosemicarbazones are synthetic compounds which are formed by the condensation of carbonyl compounds with thiosemicarbazides. In thiosemicarbazone, sulphur (S) and nitrogen (N) as donor atoms which are the combination of hard soft donor character and having versatile co-ordination character. They have many chemical, biological and medical properties e.g., antiviral. Thiosemicarbazones are believed to inhibit ribonucleotide reductase, a necessary enzyme for DNA synthesis, as part of their anticancer properties. As a viral enzyme involved in DNA synthesis and a major target for the production of anticancer drugs, ribonucleotide reductase transforms ribonucleotides into deoxy ribonucleotides. All of the compounds (1-26) had greater inhibitory effects on the cancer cell lines MCF-7, A431, A549, MDA-MB-231, and PNT-2 than the positive control (DMSO), with IC50 values for MCF-7 (IC50; 2.93 µM, 2), A431 (IC50; 4.80 µM, 3), A549 (IC50; 2.52 µM, 3), MDA-MB-231 (IC50; 2.47 µM, 20) and PNT-2 (IC50; 2.54 µM, 20). In this study, a series of 5-substituted (-OMe, -OH) and 5,7-disubstituted (-Br) N(4)-thiosemicarbazones were synthesized and analyzed by elemental analysis, FTIR, 1H-NMR, 13C-NMR, ESI-HRMS, UV-Vis, and single crystal X-ray crystallography. The CHN, UV-Vis, and ESI-HRMS data all agreed with the hypothesized structures.