Prospects of Topoisomerase Inhibitors as Promising Anti-Cancer Agents

Abstract

Topoisomerases are very important enzymes that regulate DNA topology and are vital for biological actions like DNA replication, transcription, and repair. The emergence and spread of cancer has been intimately associated with topoisomerase dysregulation. Topoisomerase inhibitors have consequently become potential anti-cancer medications because of their ability to obstruct the normal function of these enzymes, which leads to DNA damage and subsequently causes cell death. This review emphasizes the importance of topoisomerase inhibitors as marketed, clinical and preclinical anti-cancer medications. In the present review, various types of topoisomerase inhibitors and their mechanisms of action have been discussed. Topoisomerase I inhibitors, which include irinotecan and topotecan, are agents that interact with the DNA-topoisomerase I complex and avert resealing of the DNA. The accretion of DNA breaks leads to the inhibition of DNA replication and cell death. On the other hand, topoisomerase II inhibitors like etoposide and teniposide, function by cleaving the DNA-topoisomerase II complex thereby effectively impeding the release of double-strand DNA breaks. Moreover, the recent advances in exploring the therapeutic efficacy, toxicity, and MDR (multidrug resistance) issues of new topoisomerase inhibitors have been reviewed in the present review.

Recent advances on the DNA interaction properties of Schiff bases and their metal complexes

“…Many anticancer drugs' primary site of action is DNA. 76 For the creation of effective chemotherapy medications, the study of how complexes of metals interact with DNA has been a major area of research. There are mainly two broad types of DNA interactions: (1) DNA cleavage and (2) DNA binding (Scheme 3).…”

Historical Perspective and Current Trends in Anticancer Drug Development

“…The accumulation of permanent DNA breaks triggers recombination/repair pathways, mutagenesis, and chromosomal translocations. If breaks in DNA exceed the cell's repair capacity, they can initiate pathways that lead to cell death [21]. Thus, etoposide converts topoisomerase II from an essential enzyme into a potent cellular toxin that fragments the genome.…”

In vitro biological studies and computational prediction-based analyses of pyrazolo[1,5-a]pyrimidine derivatives

“… 28 (V) Plant alkaloid topoisomerase inhibitors include mitoxantrone and teniposide; these drugs inhibit the separation of the two DNA strands through interaction with topoisomerase enzymes. 29 (VI) Mitotic inhibitors include paclitaxel and docetaxel; these drugs prevent cell mitosis. 30 …”