anti-HIV Activity Research Articles

Efektivitas Farmakologi Senyawa Aktif Tumbuhan Mangrove Yang Hidup Di Indonesia

Mangroves are ecologically important plants in marine habitats that occupy the coastlines of several countries. Apart from their primary ecological importance, various parts of mangroves are widely used in traditional medicine and are claimed to be effective in treating various diseases. At present, no comprehensive effort has been made to compile and critically analyze the published literature in view of its ethnopharmacological utility. This review aims to provide a comprehensive overview of the biodiversity and distribution of mangrove plants, ethnopharmacology, phytochemical profiles, and pharmacological activities of mangrove plants used as traditional medicine in Indonesia. The method used is by using literature studies from the Science Direct, Pubmed, and Google Scholar database. Result show that In Indonesia, there are 33 types of mangrove species, all of which are traditionally used as medicine, which are spread throughout the archipelago in Indonesia. Bioactive compounds obtained from mangrove plants include polyphenols, flavonoids, alkaloids, carotenoids, tannins, saponins, steroids, amino acids, carbohydrates, proteins, vitamins etc. This review also shows that the pharmacological activities of mangrove plants in general include antimicrobials (such as antibacterial, antiviral and antifungal), anti-inflammatory, anti-ulcer, antidiarrheal, anticancer, antidiabetic, anti-HIV, antinociceptive, hepatoprotective, antiarthritis, analgesic, antioxidant and cytotoxic activities.

Anti-HIV activity of methanolic and aqueous extracts of fifteen materials of beach-cast macroalgae: valorization of underused waste biomass

ABSTRACT Beach-cast seaweeds are unexplored feedstock with plentiful biomass in some localities that could be exploited as important sources of natural products. This study evaluated the potential of beach-cast seaweed extracts to inhibit the reverse transcriptase enzyme of the HIV-1. In general, the aqueous extracts showed better biotechnological potential as an antiviral agent than methanolic extracts with lower values of IC50. However, both extracts from Alsidium seaforthii, Osmundaria obtusiloba, Dictyopteris jolyana, and Zonaria tournefortii were highly promising, reaching inhibition above 90%, as well the aqueous extract of Spyridia clavata. Macroalgae are characterized by high levels of sulphated polysaccharides, such as the carrageenan and agar sulphated galactans in red algae, fucans and fucoidans in brown algae, and heterofucans in green algae, which have been related to antiviral biological activity. Furthermore, polyphenols and tannins have been reported as the main metabolites responsible for high antiviral activity in methanol extracts from red and brown algae. One or a combination of these compounds could explain our findings. Nowadays, there is a demand in the industrial and pharmaceutical sectors for natural products with potential bioactivity and beach-cast seaweeds could be a renewable, economically viable, and abundant resource for biotechnological approaches. Therefore, this research could help multiple UN SDGs as 1 (no poverty), 3 (good health and well-being), 5 (gender equality), 6 (clean water and sanitation), 8 (decent work and economic growth), 9 (industry, innovation, and infrastructure), 10 (reduced inequalities), 11 (sustainable cities and communities), 12 (responsible consumption and production), 13 (climate action), 14 (life below water), 17 (partnerships for the goals) through the integration of sustainable use of marine resources benefiting local communities, especially female equality, human and ecosystem health and sustainable consumption and development.

Schisanwilsonins H and I, two new dibenzocyclooctane lignans from the fruits of Schisandra wilsoniana

Two new dibenzocyclooctane lignans, schisanwilsonins H (1) and I (2), together with eight known compounds gomisin J (3), wulignan A1 (4), gomisin S (5), tigloylgomisin P (6), gomisin O (7), (-)-gomisin K1 (8), rubschisantherin (9) and wuweizisu C (10) were isolated from the 95% ethanol extract of the fruits of Schisandra wilsoniana. 7 exhibited anti-HBV activity with potency against HBsAg and HBeAg secretion by 37.1% and 32.6%, respectively, at 50 μg/ml. 10 exhibited anti-HIV activity with EC50 and therapeutic index (TI) values of 2.10 μg/ml and 11.98, respectively.

Bombax ceiba plant

Plants have been an important source of medicines since the beginning of cultivation. There is a growing demand for plant-based medicines, health products, pharmaceuticals, food supplements, cosmetics etc. Bombax ceiba Linn. (Bombacaceae) is a tall tree buttressed at the base that is widely distributed throughout India, Ceylon and Malaya, upto 1500 m of altitude. Many parts of the plant (root, stem bark, gum, leaf, prickles, flower, fruit, seed and heartwood) are used by various tribal communities and forest dwellers for the treatment of a variety of ailments. The plant literature survey shows the plant possesses astringent, cooling, stimulant, diuretic, aphrodisiac, demulcent, and tonic effects and also helps in dysentery. It also possesses important pharmacological activity such as aphrodisiac, anti-inflammatory and hepatoprotective activity in addition to anticancer and anti-HIV activity, anti-Helicobacter pylori, antiangiogenic, analgesic and antioxidant activity and hypotensive, hypoglycemic and antimicrobial activity. It is reported to contain important phytoconstituents such as naphthol, naphthoquinones, polysaccharides, anthocyanins, shamimin and lupeol.

HIV-1 Integrase Inhibitory Effects of Major Compounds Present in CareVid™: An Anti-HIV Multi-Herbal Remedy.

In our continued study on the anti-HIV activity of compounds present in CareVidTM, we report the HIV-1 integrase ((HIV-1 IN) inhibitory effects of pellitorine (1), oleuropein (2), magnoflorine (3), crotepoxide (4), ent-kaurane-16β,17-diol (5), crotocorylifuran (6), lupeol (7), betulin (8), and ellagic acid (9) in an in vitro enzyme assay, and in an in silico study. Ellagic acid, pellitorine, lupeol, and betulin showed an in vitro percentage inhibition against HIV-1 IN of 21.1%, 19.0%, 18.5%, and 16.8%, respectively, at a standard concentration of 25 μg/mL. However, from a pharmacokinetic perspective, ellagic acid has poor bioavailability, due to rapid elimination in metabolism in the gut microbiome. It was postulated that known gut catabolites of ellagic acid, urolithin A (10) and urolithin B (11) could be more promising candidates in exploring the anti-HIV activity of ellagic acid-rich medicinal species consumed orally. On the contrary, urolithin A and urolithin B demonstrated lower activity with comparison to ellagic acid. The binding affinity of compounds 1–9, urolithin A, and urolithin B against the catalytic domain of HIV-1 IN was also explored by in silico methods. Docking studies showed oleuropein as the best candidate, with a predicted energy of binding of ΔG −5.81 kcal/mol, while ellagic acid showed moderate predicted inhibition (ΔG −4.38 kcal/mol) caused by the interaction between the carbonyl and the key Mg2+ ion in the active site.

Phyto-Carbazole Alkaloids from the Rutaceae Family as Potential Protective Agents against Neurodegenerative Diseases.

Plant-derived (phyto) carbazole alkaloids are an important class of compounds, presented in the family of Rutaceae (Genera Murraya, Clausena, Glycosmis, Micromelum and Zanthoxylum). Due to several significant biological activities, such as antitumor, antibacterial, antiviral, antidiabetic, anti-HIV and neuroprotective activities of the parent skeleton (3-methylcarbazole), carbazole alkaloids are recognized as an important class of potential therapeutic agents. Neurodegenerative diseases (NDs) may exhibit a vast range of conditions, affecting neurons primarily and leading ultimately to the progressive losses of normal motor and cognitive functions. The main pathophysiological indicators of NDs comprise increasing atypical protein folding, oxidative stresses, mitochondrial dysfunctions, deranged neurotransmissions and neuronal losses. Phyto-carbazole alkaloids can be investigated for exerting multitarget approaches to ameliorating NDs. This review presents a comprehensive evaluation of the available scientific literature on the neuroprotective mechanisms of phyto-carbazole alkaloids from the Rutaceae family in ameliorating NDs.

Cytotoxicity and anti-HIV activities of extracts of the twigs of Croton dichogamus\xa0Pax

BackgroundAcquired immunodeficiency syndrome (AIDS) is a clinical syndrome resulting from infection with human immunodeficiency virus (HIV), which causes profound immunosuppression. Anti-HIV drugs that are currently available are chemically synthesized and are frequently limited by side effects, the emergence of drug resistance, affordability, and availability, with over 5 million people in the world lacking access to treatment. As a result, to discover new anti-HIV agents, we investigated the effects of Kenyan C. dichogamus extracts on the laboratory-adapted strain HIV-1IIIB in human T-lymphocytic MT-4 cells.MethodsFour soluble fractions of 1:1 v/v CH2Cl2:MeOH extract of the twigs of C. dichogamus Pax were tested for their replication inhibition activity against the laboratory-adapted strain HIV-1IIIB in the human T-lymphocytic MT-4 cell line. The plant extracts were further evaluated for their cytotoxicity in MT-4 cells using the MTT assay.ResultsThe cytotoxicity CC50 values of the methanol and methylene chloride soluble fractions of C. dichogamus were found to be between 19.58 ± 0.79 and 167 ± 0.8 µg/ml, respectively. The hexane, methylene chloride, and methanol soluble fractions of the 1:1 v/v CH2Cl2:MeOH extract of the twigs of C. dichogamus showed inhibition of the HIV-1IIIB laboratory-adapted strain in a virus-infected cell culture antiviral assay. The methanol soluble fraction of the 1:1 v/v CH2Cl2:MeOH extract of the twigs of C. dichogamus showed significant anti-HIV activity by inhibiting more than 90% of viral-induced cytopathic effects with an IC50 value of 0.06 ± 0.01 µg/ml, giving an SI of 318.5.ConclusionBased on our findings, the methanol soluble fraction of the 1:1 v/v CH2Cl2:MeOH extract of the twigs of C. dichogamus has shown potential efficacy in inhibiting viral replication and could be considered a promising candidate for further studies.

2-Methoxy-6-Acetyl-7-Methyljuglone: A Bioactive Phytochemical with Potential Pharmacological Activities.

Natural products have been the focus of biomedical and pharmaceutical research to develop new therapies in recent years. 2-methoxy-6-acetyl-7-methyljuglone (2-methoxystypandrone, MAM) a natural bioactive juglone derivative, is known to have various levels of pharmacotherapeutic efficacies as an anti-inflammatory, anticancer, antioxidant, antimicrobial, and anti-HIV activities. MAM fights cancer progression by inducing apoptosis, necroptosis and deregulating signaling pathways through H2O2-induced JNK/iNOS/NO and MAPK, ERK1/2 pathways, JNK activation, and the RIP1/RIP3 complex. In this review, we summarize the pharmacological importance of MAM in the field of drug discovery. Furthermore, this review not only emphasizes the medicinal properties of MAM, but also discusses its potential efficacy in future medicinal products.

Chemical Diversity and Bioactivity of Marine Sponges of the Genus Oceanapia: A Review

: The marine sponges of the genus Oceanapia sp. is comprised of more than 50 species and are distributed in the seas around the tropical and subtropical regions. They are mainly found in the northern Indian oceans, Japan, and the south pacific coast. They are highly colored and known to be a rich source of various secondary metabolites, particularly, alkaloids. Several other secondary metabolites were also reported from this genus which include terpenes, sphingolipids, ceramides, cerebrosides, acetylenic acids, and thiocyanatins, etc. Many of these compounds isolated from this genus exhibited various biological properties including anticancer, antimicrobial, anti-HIV, ichthyotoxicity and nematocidal activities. Although several secondary metabolites have been reported from this genus, a dedicated review of the chemicals and biological activities of this genus is so far lacking. Keeping this in mind this review describes the various chemical entities isolated from the sponges of the genus Oceanapia detailing their chemical structures along with their reported biological properties.

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of Erythrina Alkaloids

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of <i>Erythrina</i> Alkaloids

Exploratory studies on soluble small molecule CD4 mimics as HIV entry inhibitors

Several small molecule CD4 mimics, which inhibit the interaction of gp120 with CD4, have been developed. Original CD4 mimics such as NBD-556, which has an aromatic ring, an oxalamide linker and a piperidine moiety, possess significant anti-HIV activity but with their hydrophobic aromatic ring-containing structures are poorly soluble in water. We have developed derivatives with a halopyridinyl group in place of the phenyl group, such as KKN-134, and found them to have excellent aqueous solubility. Other leads that were examined are YIR-821, a compound with a cyclohexane group in a spiro attachment to a piperidine ring and a guanidino group on the piperidine nitrogen atom, and its PEGylated derivative, TKB-002. YIR-821 and TKB-002 retain potent anti-HIV activity. Here, new CD4 mimics, in which the phenyl group was replaced by a halopyridinyl group with the halogen atoms in different positions, their derivatives without a cyclohexane group on the piperidine ring and their hybrid molecules with PEG units were designed and synthesized. Some of these compounds show significantly higher aqueous solubility with maintenance of certain levels of anti-HIV activity. The present data should be useful in the future design of CD4 mimic molecules.

Synthesis and anti-HIV activity of a new isoxazole containing disubstituted 1,2,4-oxadiazoles analogs

Continuing on our antiviral drug discovery research, we intended to diversify our lead anti-HIV-1 inhibitor by non-classical isosteric replacement of amide to 1,2,4-oxadiazoles. The resulting molecules isoxazole-1,2,4-oxadiazole analogs were synthesized using mild bases in ethanol under microwave irradiation. The anti-HIV potential was checked in human CD4+ reporter cell lines, TZM-bl and CEM-GFP, at the highest non-cytotoxic concentration (HNC), demonstrating that 3-((3-(p-tolyl)isoxazol-5-yl)methyl)-1,2,4-oxadiazole and 3-((3-(4-chlorophenyl)isoxazol-5-yl)methyl)-1,2,4-oxadiazole inhibit HIV-1 replication significantly and could be considered as a new lead candidate against HIV-1.

Medicinal significance of novel coumarin analogs: Recent studies

Coumarin is a versatile scaffold with outstanding biological potential and played a key role in the field of medicine. The benzopyran-2-one ring bearing heterocycles are known for antimicrobial, anti-cancer, and antioxidant activities. This review article provides the recent clinical significance reports of coumarin and coumarin-fused heterocycles. Further, this review focus on the key feature of coumarin derivatives like antimicrobial, antimalarial, anti-HIV, anti-cancer, anti-tubercular, and antioxidant activities. The above activities make this molecule a more fascinating scaffold for the invention of new novel analogs.

A Combined Approach of Pharmacophore Modeling, QSAR Study, Molecular Docking and In silico ADME/Tox Prediction of 4-Arylthio & 4-Aryloxy-3- Iodopyridine-2(1H)-one Analogs to Identify Potential Reverse Transcriptase Inhibitor: Anti-HIV Agents.

Reverse transcriptase is an important therapeutic target to treat AIDS caused by the Human Immunodeficiency Virus (HIV). Despite many effective anti-HIV drugs, reverse transcriptase (RT) inhibitors remain the cornerstone of the drug regimen to treat AIDS. In the present work, we have expedited the use of different computational modules and presented an easy, costeffective, and high throughput screening method to identify potential reverse transcriptase inhibitors. A congeneric series of 4-Arylthio & 4-Aryloxy-3- Iodopyridine-2(1H)-one analogs having anti-HIV activity were subjected to structure-based 2D, 3D QSAR, Pharmacophore Modeling, and Molecular Docking to elucidate the structural properties required for the design of potent HIV-RT inhibitors. Prediction of preliminary Pharmacokinetic and the Drug Likeliness profile was performed for these compounds by in silico ADME study. The 2D and 3D- QSAR models were developed by correlating two and three-dimensional descriptors with activity (pIC50) by sphere exclusion method and k-nearest neighbor molecular field analysis approach, respectively. The significant 2D- QSAR model developed by Partial Least Square is associated with the Sphere Exclusion method (PLS-SE), having r2 and q2 values 0.9509 and 0.8038, respectively. The 3D-QSAR model by Step Wise variable selection method (SW-kNN MFA) is more significant, which has a cross-validated squared correlation coefficient q2= 0.8509 and a non-crossvalidated correlation coefficient pred_r2= 0.8102. The pharmacophore hypothesis was developed, which comprised 5 features includes 3 aliphatic regions (Ala), 1 H-bond donor (HDr) and 1 H-bond acceptor (HAc). Docking studies of the selected inhibitors with the active site of reverse transcriptase enzyme showed hydrogen bond and π - π interaction with LYS-101, LYS-103, TYR- 181, TYR-188 and TRP-229 residues present at the active site. All the candidates with good bioavailability and ADMET drug likeliness properties. The results of the present work provide more useful information and important structural insights for the discovery, design of novel and potent reverse transcriptase inhibitors with high therapeutic windows in the future.

Recent Advances in the Discovery and Development of Anti-HIV Natural Products.

Acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) infection is a serious public problem threatening global health. At present, although "cocktail therapy" has achieved significant clinical effects, HIV still cannot be completely eradicated. Furthermore, long-term antiviral treatment has caused problems such as toxic side effects, the emergence of drug-resistant viruses, and poor patient compliance. Therefore, it is highly necessary to continue to search for high-efficient, low-toxic anti-HIV drugs with new mechanisms. Natural products have the merits of diverse scaffolds, biological activities, and low toxicity that are deemed the important sources of drug discovery. Thus, finding lead compounds from natural products followed by structure optimization has become one of the important ways of modern drug discovery. Nowadays, many natural products have been found, such as berberine, gnidimacrin, betulone, and kuwanon-L, which exert effective anti-HIV activity through immune regulation, inhibition of related functional enzymes in HIV replication, and anti-oxidation. This paper reviewed these natural products, their related chemical structure optimization, and their anti-HIV mechanisms.

Antinociceptive Activity of Syzygium Aromaticum Linn. Flower Buds (Clove) Extract and its Fractions

Syzygium aromaticum (Myrtaceae) flower buds (clove) are traditionally known to possess antimicrobial, antiprotozoal, antiviral and other activities, including the antinociceptive action. Scientific evidence also suggests the antileishmanial, antiherpetic and anti-HIV activities of the buds. This paper reports the antinociceptive activity of S. aromaticum flower buds, reinforcing its use in decreasing the pain. The present study was designed to confirm the analgesic activity of S. aromaticum extract and seven of its fractions to reveal the common belief in its painkilling effects. We chose two thermal nociception assays (i) hot–plate test (ii) and tail-flick method as our experimental techniques. Both of these methods are well established to screen anti-nociceptive activities in new molecules. The standard drug indomethacin (5 mg/kg) given by intra-peritoneal route was used in the study for comparison. The study has shown that the methanolic extract (SA-EXT) and its active fractions possess anti-nociceptive activity (pandlt;0.05) in the models of nociception used.

Retrovirus Drugs-Loaded PEGylated PAMAM for Prolonging Drug Release and Enhancing Efficiency in HIV Treatment.

Polyamidoamine dendrimer (PAMAM) with its unique characteristics emerges as a potential drug delivery system which can prolong releasing time, reduce the side effects but still retaining treatment efficiency. In this study, methoxy polyethylene glycol modified PAMAM generation 3.0 (G3.0@mPEG) is prepared and characterized via 1H-NMR, FT-IR, and TEM. Subsequently, two antiretroviral agents (ARV) including lamivudine (3TC) and zidovudine (AZT) are individually encapsulated into G3.0@mPEG. The drug-loading efficiency, drug release profile, cytotoxicity and anti-HIV activity are then evaluated. The results illustrate that G3.0@mPEG particles are spherical with a size of 34.5 ± 0.2 nm and a drug loading content of about 9%. Both G3.0@mPEG and ARV@G3.0@mPEG show no cytotoxicity on BJ cells, and G3.0@mPEG loading 3TC and AZT performs sustained drug release behavior which is best fitted with the Korsmeyer–Peppas model. Finally, the anti-HIV activity of ARV via Enzymatic Assay of Pepsin is retained after being loaded into the G3.0@mPEG, in which about 36% of pepsin activity was inhibited by AZT at the concentration of 0.226 mM. Overall, PAMAM G3.0@mPEG is a promising nanocarrier system for loading ARV in HIV treatment and prevention.

Therapeutic properties of Cinnamon Verum with special references to Hypoglcemic activity: An overview

In millennia, medicinal plants have gained greater interest owing to the presence of a broad spectrum of bioactive compounds which possess potential health benefits. Among these functional plants, cinnamon verum has captured more attention due to its multiple medicinal activities. In this review article, efforts were made to overview the functional properties of cinnamon verum with special reference to type II diabetes. Literature demonstrated that cinnamon verum possesses different pharmaceutical activities such as antioxidant, antibacterial, anti-inflammatory, anticancer, antidiabetic, wound recuperating, anti-HIV, anti-anxiety, and antidepressant activities. Moreover, hypoglycemic activity of cinnamon verum is attributed to the presence of various bioactive compounds especially cinnamaldehyde and other components of extract and essential oil.

Cell membrane-anchored anti-HIV single-chain antibodies and bifunctional inhibitors targeting the gp41 fusion protein: new strategies for HIV gene therapy

ABSTRACT Emerging studies indicate that infusion of HIV-resistant cells could be an effective strategy to achieve a sterilizing or functional cure. We recently reported that glycosylphosphatidylinositol (GPI)-anchored nanobody or a fusion inhibitory peptide can render modified cells resistant to HIV-1 infection. In this study, we comprehensively characterized a panel of newly isolated HIV-1-neutralizing antibodies as GPI-anchored inhibitors. Fusion genes encoding the single-chain variable fragment (scFv) of 3BNC117, N6, PGT126, PGT128, 10E8, or 35O22 were constructed with a self-inactivating lentiviral vector, and they were efficiently expressed in the lipid raft sites of target cell membrane without affecting the expression of HIV-1 receptors (CD4, CCR5 and CXCR4). Significantly, transduced cells exhibited various degrees of resistance to cell-free HIV-1 infection and cell-associated HIV-1 transmission, as well as viral Env-mediated cell–cell fusion, with the cells modified by GPI-10E8 showing the most potent and broad anti-HIV activity. In mechanism, GPI-10E8 also interfered with the processing of viral Env in transduced cells and attenuated the infectivity of progeny viruses. By genetically linking 10E8 with a fusion inhibitor peptide, we subsequently designed a group of eight bifunctional constructs as cell membrane-based inhibitors, designated CMI01∼CMI08, which rendered cells completely resistant to HIV-1, HIV-2, and simian immunodeficiency virus (SIV). In human CD4+ T cells, GPI-10E8 and its bifunctional derivatives blocked both CCR5- and CXCR4-tropic HIV-1 isolates efficiently, and the modified cells displayed robust survival selection under HIV-1 infection. Therefore, our studies provide new strategies for generating HIV-resistant cells, which can be used alone or with other gene therapy approaches.

Anti-HIV Compounds from the Deep-Sea-Derived Fungus Chaetomium globosum.

Chemical investigation on the deep-sea-derived fungus Chaetomium globosum led to the isolation of nine compounds. By extensive analyses of the 1D and 2D NMR as well as HR-ESI-MS spectra, their structures were elucidated as xylariol A (1), 1,3-dihydro-4,5,6-trihydroxy-7-methylisobenzofuran (2), epicoccone B (3), epicoccolide B (4), chaetoglobosin G (5), chaetoglobosin Fex (6), cochliodone A (7), cochliodone B (8), and chaetoviridin A (9), assorting as four phenolics (1-4), two cytochalosans (5-6), and three azaplilones (7-9). Compounds 1-3 were firstly reported from C. globosum. Under the concentrations of 20 μg/mL, 1, 2, and 3 exhibited potent in vitro anti-HIV activity with the inhibition rates of 70 %, 75 %, and 88 %, respectively.