Title:Coumarins as Potential Inhibitors of DNA Polymerases and Reverse Transcriptases. Searching New Antiretroviral and Antitumoral Drugs
VOLUME: 12 ISSUE: 2
Author(s):Hugo A. Garro and Carlos R. Pungitore
Affiliation:Department of Chemistry, Faculty of Chemistry, Biochemistry and Pharmacy. University of San Luis, P.O. 5700, San Luis, Argentine. `
Keywords:Cancer, coumarins, DNA polymerase, inhibitors, in silico, HIV, reverse transcriptase.
Abstract:Human Immunodeficiency Virus (HIV) is the viral agent of
Acquired Immunodeficiency Syndrome (AIDS), and at present, there is no
effective vaccine against HIV. Reverse Transcriptase (RT) is an essential
enzyme for retroviral replication, such as HIV as well as for other RNA
infectious viruses like Human T lymphocyte virus. Polymerases act in
DNA metabolism, modulating different processes like mitosis, damage repair, transcription and
replication. It has been widely documented that DNA Polymerases and Reverse Transcriptases serve as
molecular targets for antiviral and antitumoral chemotherapy. Coumarins are oxygen heterocycles that
are widely distributed throughout the plant kingdom. Natural coumarins have attraction due to their
bioactive properties such as tumor promotion inhibitory effects, and anti-HIV activity. Coumarins and
derivates exhibit potent inhibitory effects on HIV-1 replication in lymphocytes and compounds isolated
from Calophyllum inophyllum or DCK derivates showed inhibitory activity against human RT.
Furthermore, natural isocoumarins isolated from cultures of fungi or hydroxycoumarins were able to
inhibit human DNA polymerase. In view of their importance as drugs and biologically active natural
products, and their medicinally useful properties, extensive studies have been carried out on the
synthesis of coumarin compounds in recent years. Non-Nucleoside Reverse Transcriptase Inhibitors
(NNRTIs), a class of antiretroviral chemotherapeutic agents, act by binding to an allosteric pocket
showing, generally, low toxicity. This work tries to summarize the investigation about natural and
synthetic coumarins with the ability to inhibit key enzymes that play a crucial role in DNA metabolism
and their possible application as antiretroviral and antitumoral agents.
