Recent Advances in the Discovery and Development of Plant-Derived Natural Coumarins and their Analogues as Anti Human Immunodeficiency Virus—Type 1 (HIV-1) Agents
TL;DR: The aim of this review is to summarize research findings for herbal medicines, especially coumarins, which are endowed with the ability to inhibit HIV.
Abstract: The acquired immunodeficiency syndrome (AIDS) is a result of human immunodeficiency virus (HIV) infection which leads to severe suppression of immune functions. AIDS is a real threat to the health of mankind, and the search for effective therapies is still of great importance. However, besides the high cost, there are adverse effects and limitations associated with chemotherapy applied. Thus, herbal medicines are frequently used as an alternative therapy by individuals living with HIV. Numerous plant-derived compounds have been evaluated for inhibitory effects on HIV replication, and many coumarins have been found to inhibit different steps in HIV replication cycle. The aim of this review is to summarize research findings for herbal medicines, especially coumarins, which are endowed with the ability to inhibit HIV.
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TL;DR: In this article, a review of antibiotic resistance strategies produced by multidrug-resistant bacteria and phytochemicals from different classes with documented antimicrobial action against resistant bacteria, either alone or in combination with traditional antibiotics is presented.
Abstract: Microbial resistance has progressed rapidly and is becoming the leading cause of death globally. The spread of antibiotic-resistant microorganisms has been a significant threat to the successful therapy against microbial infections. Scientists have become more concerned about the possibility of a return to the pre-antibiotic era. Thus, searching for alternatives to fight microorganisms has become a necessity. Some bacteria are naturally resistant to antibiotics, while others acquire resistance mainly by the misuse of antibiotics and the emergence of new resistant variants through mutation. Since ancient times, plants represent the leading source of drugs and alternative medicine for fighting against diseases. Plants are rich sources of valuable secondary metabolites, such as alkaloids, quinones, tannins, terpenoids, flavonoids, and polyphenols. Many studies focus on plant secondary metabolites as a potential source for antibiotic discovery. They have the required structural properties and can act by different mechanisms. This review analyses the antibiotic resistance strategies produced by multidrug-resistant bacteria and explores the phytochemicals from different classes with documented antimicrobial action against resistant bacteria, either alone or in combination with traditional antibiotics.
48 citations
TL;DR: The objective of this review is to evaluate data on coumarins’ potent activity with respect to the inhibition of HIV-reverse transcriptase, HIV-integrase or HIV-protease.
Abstract: Considerable progress has been made in recent years in the field of drug development against HIV. Many different kinds of natural products, including coumarins, have been found to be active in anti-HIV models and are thus undergoing further investigation. This review demonstrates the variety of coumarins with unique mechanisms of action in the different stages of HIV replication. The discovery and development of coumarins as anti-HIV agents has expanded in the past two decades. Most of the studies have been focused on the inhibitory activity of reverse transcriptase, but anti-integrase and antiprotease activities were also described. The objective of this review is to evaluate data on coumarins’ potent activity with respect to the inhibition of HIV-reverse transcriptase, HIV-integrase or HIV-protease. Recent requirements for potential anti-HIV agents increasingly require adequate definition of the mechanism of action as well as definition of toxic effects and this also applies to natural as well as synthe...
21 citations
Cites background from "Recent Advances in the Discovery an..."
...1 μM* RT [4,5]...
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...3 μM¶,# RT [4,5]...
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...2 μM*,‡,§ RT [4,5]...
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...The coumarins represent a unique class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) [4,5]....
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...Imperatorin 100 μg/ml** RT [4,5]...
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TL;DR: The cerium Ce(III, lanthanum La(III), and neodymium Nd(III) complexes were synthesized and studied for the first time for cytotoxicity (on MT-2 cells) and as anti-HIV agents under acute and chronic infection.
Abstract: The cerium Ce(III), lanthanum La(III), and neodymium Nd(III) complexes with 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one (warfarin) (W) and 3,3'-benzylidenebis[4-hydroxycoumarin] (1) were synthesized and studied for the first time for cytotoxicity (on MT-2 cells) and as anti-HIV agents under acute and chronic infection. The complexes were characterized by different physicochemical methods: mass spectrometry, (1)H NMR, (13)C NMR, and IR spectroscopy. The spectra of the complexes were interpreted on the basis of comparison with the spectrum of the free ligands. Anti-HIV effect of the complexes/ligands was measured in MT-2 cells by microtiter infection assay. Detection of endogenous reverse transcriptase (RT) activity and RT processivity by PCR indicative for proviral DNA synthesis demonstrated that anti-HIV activity has not been linked to early stages of viral replication. No effect on late steps of viral replication has been found using cells chronically producing HIV-1(LAI) virus. La(W) demonstrated anti-HIV activity (IC50=21.4 muM) close to maximal nontoxic concentration. Nd(W), Ce(1), and Nd(1) demonstrated limited anti-HIV potency, so none of the complexes seems appropriate to be used in clinic. Further targeting of HIV-1 inhibition by La(W) is under progress.
20 citations
Cites background from "Recent Advances in the Discovery an..."
...Coumarins and bicoumarins are widely spread in nature [1, 2]....
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07 Mar 2011
TL;DR: In this article, a new reaction in phosphorus chemistry, namely, the interaction of 2,2,2-trihalobenzo-1, 3, 2-dioxaphospholes with aryl(alkyl)acetylenes, leads to the formation of benzo[e]-1,2oxaphosphinine derivatives, or “phosphacoumarins.
Abstract: The account covers a new reaction in phosphorus chemistry, namely, the interaction of 2,2,2-trihalobenzo-1,3,2-dioxaphospholes with aryl(alkyl)acetylenes, which leads to the formation of benzo[e]-1,2-oxaphosphinine derivatives, or “phosphacoumarins.” The easy formation of a P-C bond and phosphoryl group, the ipso-substitution of the oxygen atom by the carbon one, and selective chlorination para to endocyclic oxygen are realized under mild conditions in this reaction. The ipso-substitution of a tertiary butyl group and a bromine atom also takes place in some cases.
11 citations
TL;DR: In this article, the minor isomer was formed as a result of substitution of the oxygen atom in the ortho position with respect to one tert-butyl group of the initial phosphole.
Abstract: 2,2,2-Tribromo-4,6-di-tert-butylbenzo-1,3,2λ5-dioxaphospholedioxaphosphole reacted with a terminal alkyne, pent-1-yne, to give a mixture of two isomeric 1,2-benzoxaphosphinine derivatives, 6,8- and 5,7-di-tert-butyl-2-bromo-4-propylbenzo-1,2λ5-oxaphosphinin-2-oxides, at a ratio of 5.9: 1. The regioselectivity of substitution of oxygen in the dioxaphosphole fragment by carbon differs from that observed previously in the reaction with 4,6-di-tert-butyl-2,2,2-trichlorobenzo-1,3,2λ5-dioxaphosphole: the minor isomer was formed as a result of substitution of the oxygen atom in the ortho position with respect to one tert-butyl group of the initial phosphole.
3 citations
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TL;DR: The methanol extract of the dried roots of Ferula sumbul afforded two furanocoumarin esters and some of the isolated compounds showed anti-HIV activity and very weak inhibition of cytokine release.
153 citations
TL;DR: The methanol extract of the dried aerial parts of Prangos tschimganica gave three new coumarin derivatives and 30 known coumarIn derivatives, which showed anti-HIV activity and were determined by using a modified Mosher's method.
Abstract: The methanol extract of the dried aerial parts of Prangos tschimganica gave three new coumarin derivatives and 30 known coumarin derivatives. Their structures were established on the basis of chemical and spectroscopic evidence. Absolute configuration of the isolated compounds were determined by using a modified Mosher's method. Some of the isolated compounds showed anti-HIV activity.
143 citations
TL;DR: Analysis of mutants used to analyze calanolide A, 1H,3H-thiazolo[3,4-a]benzimidazole(4i), and the acyclic nucleoside analog 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine suggest that all three drugs interact with HIV-1 RT within the previously defined common binding site for nonnucleoside inhibitors.
Abstract: A number of chemically distinct nonnucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have been reported. Several lines of evidence, including the isolation of RT mutants that show cross resistance, suggest that, despite their structural diversity, many of these inhibitors bind to a common site on HIV-1 RT. We have recently reported that, on the basis of analyses of HIV-1/HIV-2 chimeras, the natural product calanolide A may interact with a different site or sites in HIV-1 RT. We have used BspMI cassette mutagenesis to prepare a collection of HIV-1 RT mutants that show resistance to the known members of the general class of nonnucleoside inhibitors. This collection of mutants can be used to determine whether a new drug will show cross resistance with known inhibitors and to define amino acid positions critical for the action of the drugs. The mutants were used to analyze calanolide A, 1H,3H-thiazolo[3,4-a]benzimidazole(4i), and the acyclic nucleoside analog 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine. These analyses suggest that all three drugs interact with HIV-1 RT within the previously defined common binding site for nonnucleoside inhibitors. However, the drugs respond differently to the panel of drug-resistant HIV-1 RTs, indicating that while the binding sites of the drugs overlap they are not identical.
123 citations
TL;DR: A variety of lectins were tested in vitro for inhibitory action against the activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the N-glycohydrolases and Agaricus bisporus lectin were the most potent.
Abstract: A variety of lectins were tested in vitro for inhibitory action against the activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the N-glycohydrolases (alpha-glucosidase, beta-glucosidase and beta-glucuronidase). Lectins from Phaseolus vulgaris, Momordica charantia, Ricinus communis and its constituent chains, and Agaricus bisporus were able to inhibit HIV-1 reverse transcriptase. P. vulgaris lectin and A. bisporus lectin were the most potent. The aforementioned lectins had only weak or no inhibitory effects on the glycohydrolases. The inhibitory effect of polysaccharopeptide from the mushroom Coriolus versicolor on HIV-1 reverse transcriptase and alpha-glucosidase was enhanced after chemical modification with chlorosulfonic acid. However, the inhibitory effect of the algal polysaccharide fucoidan on HIV-1 reverse transcriptase and alpha-glucosidase was not augmented by sulfation. Trypsin inhibitors from Phaseolus lunatus and Glycine max, gossypol and alkaloids from Corydalis yanhusuo were able to inhibit HIV-1 reverse transcriptase. Dicoumarol was capable of inhibiting HIV-1 reverse transcriptase, alpha-glucosidase, beta-glucosidase and beta-glucuronidase.
113 citations