Emerging Role of Natural Topoisomerase Inhibitors as Anticancer agents

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Pharmacology

Background:

• DNA topoisomerases (I and II) are crucial enzymes in DNA replication and repair.
• Current topoisomerase-targeting anticancer drugs function by inducing replication fork arrest and DNA breaks.
• These drugs can cause significant side effects, including cardiotoxicity and secondary malignancies.

Purpose of the Study:

• To review recent advancements in topoisomerase inhibitors for cancer treatment.
• To explore novel strategies for developing safer and more effective topoisomerase-targeting anticancer agents.
• To discuss the mechanisms of action and structural insights into topoisomerase-drug interactions.

Main Methods:

• Analysis of scientific literature on topoisomerase inhibitors published in the last decade.
• Review of studies on the structural basis of topoisomerase-drug-DNA ternary complexes.
• Examination of research into isoform-specific inhibitors and catalytic inhibitors.

Main Results:

• Topoisomerase poisons induce DNA damage, leading to cancer cell death.
• Understanding ternary complex structures aids in designing targeted inhibitors.
• Development of isoform-specific Topoisomerase II inhibitors offers potential for reduced toxicity.
• Exploration of inactive enzyme conformations and bacterial inhibitors presents new avenues.

Conclusions:

• Targeting DNA topoisomerases remains a key strategy in cancer chemotherapy.
• Future research emphasizes developing safer, isoform-specific, and catalytic inhibitors.
• Interdisciplinary efforts in chemistry and biology are vital for discovering novel topoisomerase-targeting compounds.