Recent advances in natural anti‐HIV triterpenoids and analogs
TL;DR: This article includes not only a comprehensive review of the recent anti‐HIV agent development from the perspective of medicinal chemistry, but also discusses structure–activity relationship analyses of the described triterpenoids.
Abstract: The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic is one of the world's most serious health challenges. Although combination antiretroviral therapy provides effective viral suppression, current medicines used against HIV cannot completely eradicate the infectious disease and often have associated toxicities and severe side effects in addition to causing drug resistance. Therefore, the continued development of new antiviral agents with diverse structures and novel mechanisms of action remains a vital need for the management of HIV/AIDS. Natural products are an important source of drug discovery, and certain triterpenes and their analogs have demonstrated potential as pharmaceutical precursors for the treatment of HIV. Over the past decade, natural triterpenoids and analogs have been extensively studied to find new anti-HIV drugs. This review discusses the anti-HIV triterpenoids and analogs reported during the period of 2009-2019. The article includes not only a comprehensive review of the recent anti-HIV agent development from the perspective of medicinal chemistry, but also discusses structure-activity relationship analyses of the described triterpenoids.
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TL;DR: In this article, a brief and systemic review for the determination of heavy metals by recently developed atomic techniques, including atomic absorption spectrometry (AAS), atomic fluorescence spectrometers (AFS), inductively coupled plasma-optical emission spectrometer (ICP-OES), and inductively coupling plasma-mass spectrometrizelization (Ip-MS), is presented.
24 citations
TL;DR: A review of the anti-HIV activity of natural and synthetic compounds, their history and mechanism of action, as well as the role of plants and their bioactive compounds as a source of new antiretroviral drugs is presented in this paper .
Abstract: The human immunodeficiency virus (HIV) is responsible for acquired immune deficiency syndrome (AIDS), one of the major pandemic diseases. Highly active antiretroviral therapy (HAART) is the standard HIV-treatment regimen that usually comprises a combination of three or more antiretroviral drugs. HIV reverse transcriptase inhibitors are the main HAART target, which involves the use of both nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, compounds affecting other aspects of HIV replication, such as virus entry and fusion or important viral enzymes, such as integrases and proteases, have also been developed. Natural compounds from different sources, like plants, microbial and marine organisms, showed promising anti-HIV activities to the point of establishing the basis for developing new drugs. Indeed, natural compounds-based therapies have the potential to become more efficient than conventional HAART, with less or no side effects. This review aims to gather and discuss the current information about the anti-HIV activity of natural and synthetic compounds, their history and mechanism of action as well as the role of plants and their bioactive compounds as a source of new anti-HIV drugs.
22 citations
TL;DR: In this article, 14 natural compounds from limonoids and terpenoids class were evaluated for their ability to inhibit the key therapeutic target proteins of SARS-CoV-2, including deacetylnomilin, ichangin, and nomilin.
19 citations
TL;DR: An overview of the existing hypotheses on HIV-neurotoxicity and the potential for the development of therapeutics to aid in the treatment of HIV-related nervous system dysfunction is provided in this paper.
7 citations
TL;DR: Betulinic acid (BA) is a pentacyclic triterpene acid present predominantly in Betula ssp (Betulaceae) and is also widely spread in many species belonging to different plant families.
Abstract: Betulinic acid (BA, 3β-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic triterpene acid present predominantly in Betula ssp. (Betulaceae) and is also widely spread in many species belonging to different plant families. BA presents a wide spectrum of remarkable pharmacological properties, such as cytotoxic, anti-HIV, anti-inflammatory, antidiabetic and antimicrobial activities, including antiprotozoal effects. The present review first describes the sources of BA and discusses the chemical strategies to produce this molecule starting from betulin, its natural precursor. Next, the antiprotozoal properties of BA are briefly discussed and the chemical strategies for the synthesis of analogues displaying antiplasmodial, antileishmanial and antitrypanosomal activities are systematically presented. The antiplasmodial activity described for BA was moderate, nevertheless, some C-3 position acylated analogues showed an improvement of this activity and the hybrid models-with artesunic acid-showed the most interesting properties. Some analogues also presented more intense antileishmanial activities compared with BA, and, in addition to these, heterocycles fused to C-2/C-3 positions and amide derivatives were the most promising analogues. Regarding the antitrypanosomal activity, some interesting antitrypanosomal derivatives were prepared by amide formation at the C-28 carboxylic group of the lupane skeleton. Considering that BA can be produced either by isolation of different plant extracts or by chemical transformation of betulin, easily obtained from Betula ssp., it could be said that BA is a molecule of great interest as a starting material for the synthesis of novel antiprotozoal agents.
7 citations
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TL;DR: A survey of the literature dealing with betulinic acid related biological properties that has appeared from the 1990's to the beginning of 2003 is reported.
Abstract: Betulinic acid is a naturally occurring pentacyclic triterpenoid and has been shown to exhibit a variety of biological activities including inhibition of human immunodeficiency virus (HIV), antibacterial, antimalarial, antiinflammatory, anthelmintic and antioxidant properties. This article reports a survey of the literature dealing with betulinic acid related biological properties that has appeared from the 1990's to the beginning of 2003. A broad range of medical and pharmaceutical disciplines are covered, including a brief introduction about discovery, phytochemical aspects, organic synthesis, anti-HIV and cytotoxic mechanisms of action. Various structural modifications carried out and their biological and pharmacokinetic profiles are also incorporated.
492 citations
"Recent advances in natural anti‐HIV..." refers background in this paper
...Betulinic acid is commonly found in some species of the family Betulaceae, while 3 is a major constituent in the bark of white‐barked birch trees with isolated yields up to 22% (dry weight) and can be easily converted synthetically to 1 in high yields.(33) Many studies have been devoted to the investigation of betulinic acid, betulin, and their derived compounds....
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TL;DR: Evaluation of anti-HIV activity with eight derivatives of 1 revealed that dihydrobetulinic acid was also a potent inhibitor of HIV replication, and there was no apparent correlation between anti-hIV activity and the inhibition of PKC among these compounds.
Abstract: Betulinic acid [1] and platanic acid [2], isolated from the leaves of Syzigium claviflorum, were found to be inhibitors of HIV replication in H9 lymphocyte cells. Evaluation of anti-HIV activity wich eight derivatives of 1 revealed that dihydrobetulinic acid [3] was also a potent inhibitor of HIV replication. The C-3 hydroxy group and C-17 carboxylic acid group, as well as the C-19 substituents, contribute to enhanced anti-HIV activity. The inhibitory activity of these compounds against protein kinase C (PKC) was also examined, since a correlation between anti-HIV and anti-PKC activities has been suggested. However, there was no apparent correlation between anti-HIV activity and the inhibition of PKC among these compounds
467 citations
"Recent advances in natural anti‐HIV..." refers background in this paper
...As early as 1994, betulinic acid (1; Figure 1) was shown to inhibit the infectivity of HIV‐1 in vitro.(11) Subsequently, numerous betulinic acid derivatives were synthesized with the goal to develop anti‐HIV drugs....
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TL;DR: In this mini-review, a summary of the antiviral effects reported for several natural products and herbal medicines is summarized.
377 citations
"Recent advances in natural anti‐HIV..." refers background in this paper
...During the last decade, much effort has been made to find effective anti‐HIV agents from natural products.(5,6) Many classes of natural product derivatives have been evaluated with varying success....
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283 citations
"Recent advances in natural anti‐HIV..." refers background in this paper
...35 nM and a selectivity index of 20 000.(14) BVM is defined as a novel strategy against HIV and termed a maturation inhibitor....
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TL;DR: The current state of knowledge about the health-promoting properties of this widespread, biologically active compound, as well as information about its occurrence and biosynthesis are presented.
Abstract: Ursolic acid (UA) is a natural terpene compound exhibiting many pharmaceutical properties. In this review the current state of knowledge about the health-promoting properties of this widespread, biologically active compound, as well as information about its occurrence and biosynthesis are presented. Particular attention has been paid to the application of ursolic acid as an anti-cancer agent; it is worth noticing that clinical tests suggesting the possibility of practical use of UA have already been conducted. Amongst other pharmacological properties of UA one can mention protective effect on lungs, kidneys, liver and brain, anti-inflammatory properties, anabolic effects on skeletal muscles and the ability to suppress bone density loss leading to osteoporosis. Ursolic acid also exhibits anti-microbial features against numerous strains of bacteria, HIV and HCV viruses and Plasmodium protozoa causing malaria.
260 citations
"Recent advances in natural anti‐HIV..." refers background in this paper
...Recently, the anti‐HIV and other pharmacological activities of ursolic acid were reviewed.(84) A new series of HIV‐1 PR inhibitors with pentacyclic triterpenoids as P2 ligands and phenylsulfonamide as P2′ ligands were F IGURE 24 Chemical structures of Compounds 103–111...
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