Coumarins as Inhibitors of HIV Reverse Transcriptase

Abstract

Acquired immunodeficiency syndrome (AIDS), a degenerative disease of the immune and central nervous systems, is an enormous world-wide health threat. No cure has been found, and research is aimed at developing chemotherapy against the causative agent, human immunodeficiency virus (HIV). Chemotherapy for AIDS has progressed steadily in the past decade. However, new, effective, and less toxic chemotherapeutic agents are still needed. Plants, particularly anti-infective or immunomodulating herbal medicines, can serve as sources of new active leads to be further developed as anti-AIDS drug candidates. A lot of structurally different natural coumarins were found to display potent anti-HIV activity and continued progress is anticipated in the discovery of new leads and in the development of these agents as potential anti-AIDS drug candidates. Recent studies based on the account of various coumarins from plant sources and their analogs--synthetic coumarins, indicate that some of them serve as potent nonnucleoside RT-inhibitors, another as inhibitors of HIV-integrase or HIV-protease. The current review demonstrates the variety of coumarins of natural plant origin and synthetic coumarins having unique mechanism of action to one of the most important stage of HIV replication (RT-inhibition). The merits of selecting potential anti-HIV agents to be used in rational combination drugs design and structure-activity relationships are discussed. The scientific community is looking actively for new drugs and combinations for treatment of HIV infection effective for first-line treatment, as well as against drug-resistant mutants.

Coumarins — An Important Class of Phytochemicals

“…Recent studies and review manuscripts regarding the coumarin scaffold describe the huge variety of biological activities that may be present in the natural coumarins [8,18,[62][63][64]. Venugopala et al (2013) presented several coumarins displaying activities such as antiinflammatory, anticoagulant, antibacterial, antifungal, antiviral, anticancer, anti-hypertensive, antitubercular, anticonvulsant, anti-adipogenic, Cytochrome P450 inhibiting, anti-hyperglycemic, antioxidant, and neuroprotective.…”

“…Venugopala et al (2013) presented several coumarins displaying activities such as antiinflammatory, anticoagulant, antibacterial, antifungal, antiviral, anticancer, anti-hypertensive, antitubercular, anticonvulsant, anti-adipogenic, Cytochrome P450 inhibiting, anti-hyperglycemic, antioxidant, and neuroprotective. Several recent reviews summarize and highlight advances in the application of coumarins, especially concerning their antioxidant and anticancer properties [62][63][64][65][66][67][68][69][70].From Calophyllum spp., it is remarkable the antiviral activity of calanolides and other related pyranocoumarins on Epstein-Barr virus and HIV [56]. As active compound of molluscicidal effects on Biomphalaria glabrata of C. brasiliense extracts were determined (-) mammea A/BB, also found in C. Verticillatum [71].…”

Design, synthesis and bioevaluation of novel umbelliferone analogues as potential mushroom tyrosinase inhibitors

“…Umbelliferone also known as 7-hydroxy coumarin is a natural product widely distributed in many familiar plants Apiaceae, Asteraceae, Hydrangeaceae and Acanthaceae. Coumarin derivatives are of great interest due to their diverse structural features and versatile biological properties, such as anti-inflammatory, antioxidant, vasorelaxant, cytotoxic, anti-HIV, antitubercular and antimicrobial [17][18][19][20][21][22] . Coumarin derivatives have been synthesized and extensively studied for their biological response, but the tyrosinase inhibitor activities of this kind of compounds have hardly ever appeared in the literature.…”

Structural Modifications on Natural-based Products: Synthetic Strategies and Biological Applications

“…[1,2] These heterocyclic compounds have already been previously described as anticancer, antiviral, anti-inflammatory, antimicrobial, enzymatic inhibitory and antioxidant agents. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Taking in account the versatility of the coumarin moiety one can thoroughly modify it to best serve one purposes. In this work, our group fused two other classes of natural products onto the coumarin skeleton, the chalcones (figure 1 -A) and the resveratrol derivatives ( figure 1 -B).…”