Synthesis and screening of thiosemicarbazide-dithiocarbamate conjugates for antioxidant and anticancer activities.

Abstract

Thiosemicarbazides (TSCs), dithiocarbamates (DTCs) and their molecular conjugates are promising drug targets. However, hybrids of DTCs with TSCs themselves are rarely investigated. Thus, studies were initiated to synthesize novel system derived from TSC-DTCs to examine their pharmacological applications. The targeted conjugates were designed and synthesized from aryl TSC and aryl DTCs in moderate to good yields. The structures of synthesized compounds were confirmed through FT-IR, 1H NMR, 13C NMR and mass spectrometry. The conjugates have been tested for antioxidant and anticancer activities. The in vitro antioxidant activity was performed using 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging assay, hydrogen peroxide scavenging assay and nitric oxide assay and was also compared with aryl DTCs and aryl TSCs to explore potential of newly synthesized hybrids. The preliminary anticancer screening for cytotoxicity was performed using brine shrimp lethality bioassay using Artemia salina shrimps. Anticancer screening was determined against NCI60 human tumor cell lines at NCI, USA. The results revealed that, newly synthesized hybrids are more active as compared to aryl DTCs and aryl TSCs. Among the tested conjugates for antioxidant screening, 3b was found to be more active than the standard ascorbic acid. The IC50 value of 3b were 8.96 ± 0.089, 10.7 ± 0.016 and 12.29 ± 0.086 μg/ml for DPPH, hydrogen peroxide scavenging assay and nitric oxide assay respectively, whereas IC50 values for standard were 11.75 ± 0.015, 12.03 ± 0.107 and 16.66 ± 0.242 μg/ml respectively. Since hybrids are more active than aryl DTCs and aryl TSCs, only newly synthesized hybrids were screened for anticancer potential. For cytotoxicity screening, compound 3b was found to be most active among synthesized conjugates with LD50 value of 33.86 μg/ml. For anticancer screening, the compounds 3c and 3d were found to be potent among synthesized series with percent growth inhibition of 22 to 44% when screened against colon cancer cell lines whereas, compound 3b showed growth inhibition of 40% for selective leukemia cell line, K-562. The compounds 3b, 3c and 3d with strong electron-withdrawing groups were found to be the most active antioxidant and anticancer agents among the synthesized conjugates.