anti-HIV Properties Research Articles

Pharmaceutical Importance and Synthetic Strategies for Imidazolidine-2-thione and Imidazole-2-thione Derivatives

Imidazole heterocycles containing oxygen or sulfur heteroatoms are of considerable pharmaceutical interest. Many synthetic strategies for imidazolidine-2-thione and imidazole-2-thione derivatives were developed in the past years. They have been well documented by a steadily increasing number of publications and patents. Substituted imidazolidine-2-thiones and imidazole-2-thiones display remarkable biological activities. For instance, imidazole-2-thione has been reported to exhibit antimicrobial, antifungal, antithyroid, antioxidant, cardiotonic, antihypertensive, Dopamine beta-Hydroxylase (DBH) inhibitory and anti-HIV properties. Imidazolidine-2-thione derivatives have been reported to exhibit antimicrobial activity, anti-HIV activity, antifungal activity and so forth. The main purpose of this review is to present a survey of the literature on the different methods of synthesis and reactions involving imidazolidine-2-thione and imidazole-2-thione during the last few decades. This article summarizes an efficient, microwave-assisted method for the liquid-phase combinatorial synthesis of 3,5-disubstituted-thiohydantoin, also reported previously. Synthesis of metal complexes of imidazolidine-2-thione and its derivatives were reported as antimicrobial agents also discussed in the article. Some of the chiral imidazolidine-2-thione N-and C-nucleoside were reported as precursors for the synthesis of azidonucleosides and fluoronucleosides known for their anti-AIDS activity. Metal complexes of heterocyclic thione ligands were reported to possess antifungal activity. Imidazolidine-2-thione and imidazole-2-thione derivatives have found applications in diverse therapeutic areas. Imidazolidine-2-thiones are also used as a chiral auxiliary and ligand for asymmetric catalysis.

Functional Analysis of C-type Lysozyme in Penaeid Shrimp

Lysozyme is an enzyme that cleaves the β-1,4-glycosidic linkages between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycan, leading to bacterial lysis. Recently, lysozyme has been found to have anti-HIV and anti-cancer properties in mammals. However, most functional analyses were done in vitro using purified or recombinant lysozyme protein. Here, we used RNA interference to silence c-type lysozyme expression in penaeid shrimp, Marsupenaeus japonicus, to analyze the function of lysozyme in vivo. Silencing of lysozyme expression by dsRNA lysozyme (dsLYZ) led to 100% mortality without any artificial bacterial infection in 5 days. Lysozyme deficiency caused the number of hemocytes in hemolymph to decrease from 1.3 × 10(7) to 2.3 × 10(6) cells/ml and caused the number of bacteria to increase from 78 to 764 colony-forming units/ml. Suppression of bacterial growth using oxytetracycline and kanamycin showed improvement in mortality, suggesting that shrimp mortality post- dsLYZ injection can be attributed to bacterial growth in the shrimp hemolymph. The majority of the bacteria, identified by 16 S rRNA analysis, were Gram-negative species such as Vibrio and Pseudomonas. Furthermore, PKH26 staining showed that the dsLYZ-injected shrimp were unable to eliminate non pathogenic Escherichia coli or Staphylococcus aureus in 24 h. These data suggest that c-type lysozyme in shrimp serves to regulate the growth of bacterial communities, particularly Gram-negative bacteria, in the hemolymph.

Ionic derivatives of betulinic acid as novel HIV-1 protease inhibitors

Betulinic acid is a natural product possessing abundant and favourable biological activity, including anti-cancer, anti-malarial, anti-inflammatory and anti-HIV properties, while causing minimal toxicity to unaffected cells. The full biological potency of betulinic acid cannot be fully unlocked, however, for a number of reasons, a primary one being its limited solubility in aqueous and biologically pertinent organic media. Aiming to improve the water solubility of betulinic acid without disrupting its structurally related bioactivity, we have prepared different ionic derivatives of betulinic acid. Inhibition bioassays on HIV-1 protease-catalysed peptide hydrolysis indicate significantly improved performance resulting from converting the betulinic acid to organic salt form. Indeed, for one particular cholinium-based derivative, its water solubility is improved more than 100 times and the half maximal inhibitory concentration (IC50) value (22 μg mL−1) was one-third that of wide-type betulinic acid (60 μg mL−1). These encouraging results advise that additional studies of ionic betulinic acid derivatives as a therapeutic solution against HIV-1 infection are warranted.

Bitter Gourd (Momordica charantia) is a Cornucopia of Health: A Review of its Credited Antidiabetic, Anti-HIV, and Antitumor Properties

Bitter gourd (Momordica charantia, BG) is both a nutritious and healthy food with a distinctive bitter flavor, and it is also widely exploited in folklore medicine. This review focuses on the efficacies and molecular mechanisms of BG-induced anti-diabetic, anti-HIV, and antitumor activities contributed by over twenty active components. The intent of this review is to provide comprehensive and valuable information for medicinal researchers, drug investigators, clinicians, and even patients with an interest in BG. In conclusion, BG is a cornucopia of health and it deserves in-depth investigations for clinical application in the future.

Molecular Classification of Commercial Spirulina Strains and Identification of Their Sulfolipid Biosynthesis Genes

Cyanobacterial strains of the genus Spirulina have recently been identified as an excellent source of sulfolipids, some of which possess anti-HIV properties. Thus, to investigate the distribution of sufolipid biosynthesis pathways in Spirulina, a genetic screening/phylogentic study was performed. Five different strains of Spirulina [Spirulina (Jiangmen), Spirulina sp., S. platensis, S. maxima, and Spirulina seawater] sourced from different locations were initially classified via 16S rDNA sequencing, and then screened for the presence of the sulfolipid biosynthesis genes sqdB and sqdX via a PCR. To assess the suitability of these strains for human consumption and safe therapeutic use, the strains were also screened for the presence of genes encoding nonribosomal peptide synthases (NRPSs) and polyketide synthases (PKSs), which are often associated with toxin pathways in cyanobacteria. The results of the 16S rDNA analysis and phylogenetic study indicated that Spirulina sp. is closely related to Halospirulina, whereas the other four Spirulina strains are closely related to Arthrospira. Homologs of sqdB and sqdX were identified in Spirulina (Jiangmen), Spirulina sp., S. platensis, and the Spirulina seawater. None of the Spirulina strains screened in this study tested positive for NRPS or PKS genes, suggesting that these strains do not produce NRP or PK toxins.

Molecular modeling, docking and dynamics simulations of GNA-related lectins for potential prevention of influenza virus (H1N1)

The Galanthus nivalis agglutinin (GNA)-related lectin family exhibit significant anti-HIV and anti-HSV properties that are closely related to their carbohydrate-binding activities. However, there is still no conclusive evidence that GNA-related lectins possess anti-influenza properties. The hemagglutinin (HA) of influenza virus is a surface protein that is involved in binding host cell sialic acid during the early stages of infection. Herein, we studied the 3D-QSARs (three-dimensional quantitative structure-activity relationships) of lectin- and HA-sialic acid by molecular modeling. The affinities and stabilities of lectin- and HA-sialic acid complexes were also assessed by molecular docking and molecular dynamics simulations. Finally, anti-influenza GNA-related lectins that possess stable conformations and higher binding affinities for sialic acid than HAs of human influenza virus were screened, and a possible mechanism was proposed. Accordingly, our results indicate that some GNA-related lectins, such as Yucca filamentosa lectin and Polygonatum cyrtonema lectin, could act as drugs that prevent influenza virus infection via competitive binding. In conclusion, the GNA-related lectin family may be helpful in the design of novel candidate agents for preventing influenza A infection through the use of competitive combination against sialic acid specific viral infection.

Design, synthesis, and biological evaluation of a biyouyanagin compound library

Modern drug discovery efforts rely, to a large extent, on lead compounds from two classes of small organic molecules; namely, natural products (i.e., secondary metabolites) and designed compounds (i.e., synthetic molecules). In this article, we demonstrate how these two domains of lead compounds can be merged through total synthesis and molecular design of analogs patterned after the targeted natural products, whose promising biological properties provide the motivation. Specifically, the present study targeted the naturally occurring biyouyanagins A and B and their analogs through modular chemical synthesis and led to the discovery of small organic molecules possessing anti-HIV and anti-arenavirus properties.

2D autocorrelation modelling of the anti-HIV HEPT analogues using multiple linear regression approaches

A quantitative structure–anti HIV-1 activity relationship study has been applied in a series of 1-[2-hydroxyethoxy-methyl]-6-(phenylthio)thymine] analogues acting as non-nucleoside reverse transcriptase inhibitors. The relevant 2D autocorrelation descriptors for deriving a quantitative relation between the anti-HIV activity and structural properties were selected by the multiple linear regression approach. Analysis of the resulting model revealed a correlation coefficient and a root mean square error of 0.859 and 0.503, respectively. The predictive ability of the model indicates that this model can be used for virtual library screening of databases for novel potent anti-HIV agents.

Antiproliferative effects of flavonoid fractions from Calendula officinalis flowers in parent and tamoxifen resistant T47D human breast cancer cells

The risk of human breast cancer is concerned to cumulative exposure of the breast cells to endogenous estrogens. Strategies aiming at reducing the production of estrogens may be useful for the prevention of estrogens-related breast cancer. Several natural products with plant origin have the potential value as chemo-preventive or therapeutic agents in cancer. Flavonoids, the natural polyphenol compounds, have shown antiviral, anti-inflammatory, anti-mutagenic and anti-carcinogenic activities. Calendula officinalis, a member of compositae family, is well known for its pharmacological effects such as anti-inflammatory, anti-viral, anti-HIV, anti-tumor, anti-mutagenic and cytotoxic properties. Mechanism of the possible chemo-preventing action of flavonoids has not been yet completely understood. They may exert their chemo-preventive and anti-carcinogenic effects in estrogen-dependent cells by inhibiting aromatase, 17?-hydroxysteroid oxidoreductase and other enzymes involved or by possessing estrogenic and anti-estrogenic activities. In this study, three major flavonoid fractions were separated from a methanol extract of Calendula officinalis flowers by preparative TLC. These fractions were evaluated for inhibition of parent and tamoxifen resistant T47D human breast cancer. The fractions did not have inhibitory effect. We also examined the effect of quercetin and isorhamnetin on the growth of parent and resistant T47D cells in the presence or absence of tamoxifen. It was found that quercetin increased cell proliferation of the resistant T47D cells at the presence of tamoxifen but no effect was detected by using quercitin itself. In consequence, isorhamnetin had not any proliferative or anti-proliferative activity on the both cell lines. Many mechanisms can contribute to the affects obtained on the cell growth.

Potential use of rapamycin in HIV infection

The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of published studies that evaluated the in vitro and in vivo activity of RAPA in HIV. RAPA represses HIV-1 replication in vitro through different mechanisms including, but not limited, to down regulation of CCR5. In addition RAPA synergistically enhances the anti-HIV activity of entry inhibitors such as vicriviroc, aplaviroc and enfuvirtide in vitro. RAPA also inhibits HIV-1 infection in human peripheral blood leucocytes-SCID reconstituted mice. In addition, a prospective nonrandomized trial of HIV patient series receiving RAPA monotherapy after liver transplantation indicated significantly better control of HIV and hepatitis C virus (HCV) replication among patients taking RAPA monotherapy. Taken together, the evidence presented in this review suggests that RAPA may be a useful drug that should be evaluated for the prevention and treatment of HIV-1 infection.

Comparative study of rosmarinic acid content in Satureja species

Satureja species are used in traditional medicine and phytotherapy mostly in gastrointestinal disorders. This genus is rich in essential oil and phenolic compounds. Rosmarinic acid which is found in this genus exhibits important biological activities such as antiviral, antioxidant, anti-inflammatory and anti HIV properties [1–3]. In this investigation, rosmarinic acid content of different Satureja species which grow in various parts of Iran was determined by using HPLC method. Aerial parts of six Satureja species named S. hortensis, S. khuzestanica, S. bakhtiarica, S. atropa, S. mutica and S. macranta were collected, identified, dried and milled. 200mg of each plant was extracted by using water, methanol and 2- propranol in a ratio of 80:10:10 as solvent. O-phosphoric acid (0.085%) was added to the solvent subsequently. The HPLC was performed by using C18 column. The mobile phase was the same as extraction solvent with gradient mode. UV spectra were collected across the range of 200–900nm, extracting 330nm for the chromatograms. The results showed that the HPLC method could separate rosmarinic acid from other components of the plants efficiently. By using above-mentioned method, rosmarinic acid content inSatureja species was found 0.12–1.90% in dried plants. The highest amount of the rosmarinic acid was found in S. mutica, whereas S. khuzestanica contained the lowest content of rosmarinic acid.

Proprotein Convertase Inhibitory Activities of Flavonoids Isolated from Oroxylum Indicum

Proprotein Convertases (PCs) or Proprotein Convertase Subtilisin/Kexins (PCSKs) belong to a family of calcium-dependent endoproteases that are structurally related to bacterial subtilisin and yeast kexin. These enzymes play major roles in the processing of inactive precursor proteins producing their bioactive mature forms that are implicated in a wide variety of diseases including cancer, viral and bacterial infections. As a result, PCs are major targets for intervention of these diseases. Our objective in this study is to find non-peptide inhibitors of PC-enzymes from a potential natural source. Herein we describe several natural flavonoid compounds as inhibitors of PC-enzymes including furin, a key member. These compounds were isolated from the medicinal plant Oroxylum indicum, fully characterized and tested in vitro for their PC-inhibitory property against the fluorogenic peptide substrate, Boc-RVRR-MCA (Boc = tert-butyloxy carbonyl, MCA = 4-methyl coumarin7-amide). The measured Ki and IC50 were found to be in low microM ranges. A comparative analysis of inhibition against furin, PC4, PC5 and PC7 suggested a partial selectivity towards PC4. These flavonoids also blocked efficiently the PC4-mediated processing of a fluorogenic peptide derived from the processing site of its substrate, pro-Insulin Growth Factor-1 (proIGF-1). This anti-protease activity may provide a rationale for the observed anticancer and anti-HIV properties of some of these flavonoid compounds. This is the first demonstration of anti-PC activity of flavonoid compounds.

Synthesis, Biological Properties and Anti-HIV-1 Activity of New Pyrimidine P1,P2-Dinucleotides

New homo- and hetero-P1,P2-dinucleotides were prepared with the use of multistep procedures starting from the monophosphates of 3′-fluoro-2-thiothymidine, 3′-fluoro-4-thiothymidine, AZT and 1-[(2-hydroxyethoxy)-methyl-5-propyl-6-phenylselenenyl]uracil. Anti-HIV properties of the synthesized P1,P2-dinucleotides were evaluated against laboratory syncytia inducing strain HIV-1 in CEM-T4 cells. Anti-HIV activities were in the range of 5–45 nM, and therapeutic indexes were higher than 4666–14000. Interactions of the above mentioned compounds with recombinant HIV-1 reverse transcriptase were also investigated. The obtained results point to reverse transcriptase inhibition, with somewhat lower inhibitory activity than that of their parental nucleoside-5′-triphosphates. Compound 6 may be regarded as a potent anti-HIV/AIDS drug.

Crystal structures of a novel anti-HIV mannose-binding lectin from Polygonatum cyrtonema Hua with unique ligand-binding property and super-structure

Polygonatum cyrtonema lectin (PCL) is a novel anti-HIV mannose-binding lectin from Galanthus nivalis agglutinin (GNA)-related lectin family. Crystal structures of ligand-free PCL and its complexes with monomannoside and alpha1-3 dimannoside have been determined. The ligand-free PCL is dimeric, with both subunits adopt the beta-prism II fold. PCL subunit binds mannose using a potential bivalent mode instead of the usual trivalent mode, in which carbohydrate-binding site (CBS) I and CBS III adopt the conserved mannose-binding motif of QXDXNXVXY (X is one of any amino acid residues) as observed in other structurally characterized GNA-related lectins, while CBS II adopts a modified motif with residues Gln58 and Asp60, which are critical for mannose-binding, substituted by His58 and Asn60, respectively. As a result, CBS II is unfit for mannose-binding. In the mannoside complexes, ligand-bindings only occur at CBS I which provides the specificity for alpha1-3 dimannoside. CBS II and CBS III are cooperatively occupied by a well-ordered sulfate ion, through which the individual dimers are cross-linked to form a unique super-structure of 3(2) helical lattice. Surveying the sequences of GNA-related lectins revealed that the modified binding motif of CBS II is widely distributed in the Liliaceae family as an intrinsic structural element. There is evidence that other GNA-related lectins will also adopt the similar super-structure as PCL. Thus PCL structure, unique in ligand-binding mode, may represent a novel type of structure of GNA-related lectins. Comparative analyses indicated that the dimer-based super-structure may play a primary role in the anti-HIV property of PCL.

“Momordica balsamina: A Medicinal and Neutraceutical Plant for Health care Management”. Comments: Biotechnological Potential of M. balsamina Revealed

This has reference to the recent review article entitled “Momordica balsamina; a medicinal and neutraceutical plant for health care management” which appeared in Current Pharmaceutical Biotechnology1. The article discussed medicinal aspect i.e. anti-HIV, anti-inflammatory, hypoglycaemic, anti-bacterial, anti-plasmodial anti-diarrheal, anti-oxidant and hepatoprotective properties of M. balsamina. It is a timely article, which deserves appreciation; however by addressing few shortcomings will make it an interesting peace of research work. I complement authors for bringing about information on this plant which has skipped major international attention. The authors have concluded many properties based on the scarcely available literature which warrants urgent attention. The statement “M. balsamina is “an” (should have been “a”) miracle wild herb with anti-HIV properties2. First of all reference citation is wrong; it should have been 69(6), 1209-1214. Most importantly this reference is about identification and characterization of human retrovirus and there is no mention in this article that M. balsamina has shown some anti-HIV properties. I apprehend that such conclusions would misguide the researchers working on this plant. Such studies, where identification and usage of biological component from M. balsamina can establish anti-HIV properties are highly desirable. Furthermore, some studies have been initiated in this direction, where a low molecular weight protein purified from this novel species of Momoridca possesses ribosome inactivation property [1], this activity may be explored against viruses but same requires validation before assigning a title “anti-HIV property”. The authors interpretation is hasty as reference cited in the article3 too endorses that the effect of M. balsamina on the virus adsorption process needs to be further assessed using more sensitive techniques. In the next paragraph on same page, authors have described Momordin I and Momordin II are ribosome inactivating proteins found in Momordica sp. However, literature also states that Momordin I is a compound that has been isolated from Ampelopsis radix, a chinese herb, and found to inactivate transcription factor activator protein (AP-1) [2]. Further, structure of Momordin I (extracted from the seeds of M. charantia) should have representation in the form of helices or coils or pleats in three dimensional forms rather than a planer structure as mentioned by authors (for Momordin structure see [3]. Moreover, the structure for Momordin II represented in Fig. (2B) (on page 669) is not shown in the cited reference4 as mentioned in the article, rather amino acid sequence has been provided (as given by authors as Fig. (4) in the same article on page 678). The structures mentioned in the article are of cucurbitane-type triterpenoids isolated from M. balsamina [4]. In such a scenario; authors have misinformed the readers about structures and same needs correction in the article. The authors expressed a lot of enthusiasm towards the application of M. balsamina proteins for combating HIV/ AIDS but problems associated with toxicities and bioavailability of these proteins limit potential usefulness in such therapies. A number of critical animal toxicological and human clinical studies are not mentioned as the same have not been carried. Most of the studies that have been carried so far are inconclusive and requires further authentication before advocating this plant as a “hidden gift of nature”.

Pradimicin S, a highly soluble nonpeptidic small-size carbohydrate-binding antibiotic, is an anti-HIV drug lead for both microbicidal and systemic use.

Pradimicin S (PRM-S) is a highly water-soluble, negatively charged derivative of the antibiotic pradimicin A (PRM-A) in which the terminal xylose moiety has been replaced by 3-sulfated glucose. PRM-S does not prevent human immunodeficiency virus (HIV) adsorption on CD4(+) T cells, but it blocks virus entry into its target cells. It inhibits a wide variety of HIV-1 laboratory strains and clinical isolates, HIV-2, and simian immunodeficiency virus (SIV) in various cell culture systems (50% and 90% effective concentrations [EC(50)s and EC(90)s] invariably in the lower micromolar range). PRM-S inhibits syncytium formation between persistently HIV-1- and SIV-infected cells and uninfected CD4(+) T lymphocytes, and prevents dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-mediated HIV-1 and SIV capture and subsequent virus transmission to CD4(+) T cells. Surface plasmon resonance (SPR) studies revealed that PRM-S strongly binds to gp120 in a Ca(2+)-dependent manner at an affinity constant (K(D)) in the higher nanomolar range. Its anti-HIV activity and HIV-1 gp120-binding properties can be dose-dependently reversed in the presence of an (alpha-1,2)mannose trimer. Dose-escalating exposure of HIV-1-infected cells to PRM-S eventually led to the isolation of mutant virus strains that had various deleted N-glycosylation sites in the envelope gp120 with a strong preference for the deletion of the high-mannose-type glycans. Genotypic resistance development occurred slowly, and significant phenotypic resistance occurred only after the sequential appearance of up to six mutations in gp120, pointing to a high genetic barrier of PRM-S. The antibiotic is nontoxic against a variety of cell lines, is not mitogenic, and does not induce cytokines and chemokines in peripheral blood mononuclear cells as determined by the Bio-Plex human cytokine 27-plex assay. It proved stable at high temperature and low pH. Therefore, PRM-S may qualify as a potential anti-HIV drug candidate for further (pre)clinical studies, including its microbicidal use.

Momordica balsamina: A Medicinal and Neutraceutical Plant for Health Care Management

Momordica balsamina, African pumpkin (Cucurbitaceae), is a tendril-bearing, wild climber containing wide spectrum of medicinal and nutritional values and has been used as a traditional folk medicine in many countries. The leaves, fruits, seeds, and bark of the plant contains resins, alkaloids, flavonoids, glycosides, steroids, terpenes, cardiac glycoside, saponins having various medicinal importance viz. anti-HIV, anti-plasmodial, shigellocidal, anti-diarrheal, anti-septic, anti-bacterial, anti-viral, anti-inflammatory, anti-microbial, hypoglycemic, antioxidant, analgesic and hepatoprotective properties. The therapeutic agent 'Momordin' is capable of inhibiting the growth of HIV and other viruses. The leaves are also important source of nutrients having 17 amino acids with adequate mineral composition like potassium, magnesium, phosphorus, calcium, sodium, zinc, manganese and iron. It also helps to combat the problem of micronutrient deficiencies in soil and high value of protein and fat with low fibre content. High potassium content is a good source for the management of hypertension and other cardiovascular conditions. This plant is being promoted as a protein supplement for cereal-based diets in poor rural communities. The commercial exploitation of this plant for biopharmaceuticals and neutraceuticals are some of the prospective future potential of this wild herb. This review discusses the potential of medicinal and nutritional importance of this wild herb for health care management.

Expression of a Modified Form of CD4 Results in the Release of an Anti-HIV Factor Derived from the Env Sequence

We have studied the inhibitory effect of a CD4 chimera (CD4epsilon15) on HIV replication. This chimera is retained in the endoplasmic reticulum and traps the HIV envelope precursor gp160, preventing its maturation. Retroviral expression of the chimera strongly inhibited HIV replication even when it is expressed by only a minority of the T cell population. This protective effect on bystander nontransduced cells is mediated by a soluble factor that we identified as a fragment of HIV gp120 envelope protein and accordingly, we named this factor Env-derived antiviral factor (EDAF). Biochemical and immunoreactivity data show that EDAF is comprised of the gp120 C3-C5 regions and indeed, a recombinant protein bearing this sequence reproduces the anti-HIV properties of EDAF. Surprisingly, three tryptic peptides derived from EDAF are homologous but not identical with the corresponding sequences of the HIV isolate used to generate EDAF. We propose that EDAF results from an alternative intracellular processing of the Env protein provoked by its association to CD4epsilon15 and the selection of the best fitted Env protein sequences contained within the HIV isolate. The presence of EDAF improves the therapeutic potential of the CD4epsilon15 gene and it opens new possibilities for antiviral treatment and vaccine development.

Comparing anti-HIV, antibacterial, antifungal, micellar, and cytotoxic properties of tricarboxylato dendritic amphiphiles

Three series of homologous dendritic amphiphiles—RCONHC(CH 2CH 2COOH) 3, 1( n); ROCONHC(CH 2CH 2COOH) 3, 2( n); RNHCONHC(CH 2CH 2COOH) 3, 3( n), where R = n-C nH 2n+1 and n = 13–22 carbon atoms—were assayed for their potential to serve as antimicrobial components in a topical vaginal formulation. Comparing epithelial cytotoxicities to the ability of these homologues to inhibit HIV, Neisseria gonorrhoeae, and Candida albicans provided a measure of their prophylactic/therapeutic potential. Measurements of the ability to inhibit Lactobacillus plantarum, a beneficial bacterium in the vagina, and critical micelle concentrations (CMCs), an indicator of the potential detergency of these amphiphiles, provided additional assessments of safety. Several amphiphiles from each homologous series had modest anti-HIV activity (EC 50 = 110–130 μM). Amphiphile 2( 18) had the best anti- Neisseria activity (MIC = 65 μM), while 1( 19) and 1( 21) had MICs against C. albicans of 16 and 7.7 μM, respectively. Two measures of safety showed promise as all compounds had relatively low cytotoxic activity (EC 50 = 210–940 μM) against epithelial cells and low activity against L. plantarum, 1( n), 2( n), and 3( n) had MICs ⩾ 490, 1300, and 940 μM, respectively. CMCs measured in aqueous triethanolamine and in aqueous potassium hydroxide showed linear dependences on chain length. As expected, the longest chain in each series had the lowest CMC—in triethanolamine: 1( 21), 1500 μM; 2( 22), 320 μM; 3( 22), 340 μM, and in potassium hydroxide: 1( 21), 130 μM; 3( 22), 40 μM. The CMC in triethanolamine adjusted to pH 7.4 was 400 μM for 1( 21) and 3900 μM for 3( 16). The promising antifungal activity, low activity against L. plantarum, relatively high CMCs, and modest epithelial cytotoxicity in addition to their anti- Neisseria properties warrant further design studies with dendritic amphiphiles to improve their safety indices to produce suitable candidates for antimicrobial vaginal products.

A Survey of Plants with Anti-HIV Active Compounds and their Modes of Action

Background: Several limitations of current antiretroviral therapy (ART) programmes will continue to push patients towards the use of plants to manage HIV/AIDS. However, evidence about the use of anti-HIV plants is anecdotal. Objectives: Search the literature for research articles that document plants with anti-HIV properties; and document the taxonomic families and species of plants with anti-HIV properties, their active ingredients, and modes of action against HIV. Methodology: Literature search for the key words “plants with anti-HIV activity” in PubMed Central. Results: The literature survey documented about 36 plant families containing 46 plant species with known anti-HIV active compounds and known modes of action. Anti-HIV active compounds such as terpenoids, coumarins, polyphenols, tannins, proteins, alkaloids, and biflavonoids inhibit various steps of the HIV life cycle. Discussion: Most studies that revealed anti-HIV active compounds and their modes of action were conducted outside Africa. A new initiative under NEPAD will help validate African medicinal plants used to manage HIV/AIDS. Conclusions: The review presents evidence that several plant families and species contain anti-HIV active compounds that could be developed into newer drugs to manage HIV/AIDS. This evidence should persuade further research and public interest into the isolation of anti-HIV active compounds from plants. Recommendation: There is an urgent need to fasttrack HIV/AIDS clinical trials of candidate drugs developed from novel compounds isolated from plants. Keywords : Plants, anti-HIV active compounds, modes of action