Design, Synthesis and biological evaluation of diazeno-thiazole derivatives as ribonucleotide reductase inhibitors

Mohd Usman Mohd Siddique, Surender Singh Jadav, Geraldine Graser, Philipp Saiko, Thomas Szekeres, Barij N Sinha, Venkatesan Jayaprakash


Ribonucleotide reductase(RNR) is a metalloenzyme that catalyses the rate limiting step in DNA synthesis and repair. It causes the reduction of ribonucleotide to 2’-deoxyribonuclotides which are used as precursors for DNA synthesis, thus offering a good target for inhibition of cell synthesis. Experimental results have been proven that RNR inhibitors can be used as antiviral, anticancer or antibacterial agents. Here we report the synthesis of a novel class of diazeno-thiazole derivatives as potent RNR inhibitors. A series of forty molecules were synthesized and evaluated for their RNR inhibitory properties. All compounds were found to be good inhibitors of the RNR. Compound 3iwas found to be most active showing an IC50 value of 0.8 µm. The established SAR study indicated the presence of a polar bridge with an adjacent flexible aromatic ringprerequisite for RNR inhibitory activity. Moreover, compounds having an additional 4-chloro phenyl ring were found to be most potent.


Ribonucleotide reductase(RNR); diazeno-thiazole derivatives; RNR inhibitor

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