Mechanism of action of key enzymes associated with cancer propagation and their inhibition by various chemotherapeutic agents.
The propagation of cancer, which is basically the consequence of uncontrolled multiplication of cells, is a complicated process involving the participation of a number of enzymes. The molecular level understanding of the chemistry of these enzymes is the starting step towards the development of anti-cancer drugs and a collective view of these enzymes (responsible for cell multiplication) could help in the development of multiple target ligands. In this review, the mechanistic chemistry of the key enzymes viz. ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase, topoisomerase II, closely involved at various stages of cell multiplication and hence responsible for the propagation of cancer, and some of their suitable inhibitors have been discussed. Further, this review will elucidate the chemistry of lactate dehydrogenase and cyclooxygenase, the enzymes responsible for providing the extra energy to the cancer cells and initiating the growth of tumors through the formation of mutagens, respectively.
Singh
Palwinder
P
Department of Chemistry, Guru Nanak Dev University, Amritsar, India. palwinder_singh_2000@yahoo.com
Bhardwaj
Atul
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D008024:Ligands; D059005:Topoisomerase II Inhibitors; D007770:L-Lactate Dehydrogenase; D011451:Prostaglandin-Endoperoxide Synthases; D012264:Ribonucleotide Reductases; D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase; D004250:DNA Topoisomerases, Type II