anti-HIV Activity Research Articles

Design, Synthesis, Biological Evaluation and Molecular Docking Studies of New Thiazolidinone Derivatives as NNRTIs and SARS-CoV-2 Main Protease Inhibitors.

HIV-1 remains a major health problem worldwide since the virus has developed drug-resistant strains, so, the need for novel agents is urgent. The protein reverse transcriptase plays fundamental role in the viruses' replication cycle. FDA approved Delavirdine bearing a sulfonamide moiety, while thiazolidinone has demonstrated significant anti-HIV activity as a core heterocycle or derivative of substituted heterocycles. In this study, thirty new thiazolidinone derivatives (series A, B and C) bearing sulfonamide group were designed, synthesized and evaluated for their HIV-1 RT inhibition activity predicted by computer program PASS taking into account the best features of available NNRTIs as well as against SARS-COV-2 main protease. Seven compounds showed good anti-HIV inhibitory activity, with two of them, C1 and C2 being better (IC50 0.18 μΜ & 0.12 μΜ respectively) than the reference drug nevirapine (IC50 0.31 μΜ). The evaluation of molecules to inhibit the main protease revealed that 6 of the synthesized compounds exhibited excellent to moderate activity with two of them (B4 and B10) having better IC50 values (0.15 & 0.19 μΜ respectively) than the reference inhibitor GC376 (IC50 0.439 μΜ). The docking studies is coincides with experimental results, showing good binding mode to both enzymes.

The Role of Peptides in Combatting HIV Infection: Applications and Insights.

Peptide-based inhibitors represent a promising approach for the treatment of HIV-1, offering a range of potential advantages, including specificity, low toxicity, and the ability to target various stages of the viral lifecycle. This review outlines the current state of research on peptide-based anti-HIV therapies, highlighting key advancements and identifying future research directions. Over the past few years, there has been significant progress in developing synthetic peptide-based drugs that target various stages of the viral life cycle, including entry and replication. These approaches aim to create effective anti-HIV therapies. Additionally, peptides have proven valuable in the development of anti-HIV vaccines. In the quest for effective HIV vaccines, discovering potent antigens and designing suitable vaccine strategies are crucial for overcoming challenges such as low immunogenicity, safety concerns, and increased viral load. Innovative strategies for vaccine development through peptide research are, therefore, a key focus area for achieving effective HIV prevention. This review aims to explore the strategies for designing peptides with anti-HIV activity and to highlight their role in advancing both therapeutic and preventive measures against HIV.

Nerium oleander Cultivation in Tamil Nadu, India: An Exploratory Study

In Indian traditional medicine, Nerium oleander is a significant medicinal herb. This plant has the potential to be fatal in many situations; poisoning cases have been documented in tropical and subtropical regions of the world, and suicide cases are common in South Asian nations, particularly in India and Sri Lanka. The plant is hazardous in all sections and contains a range of cardiac glycosides, such as gentiobiosyl, neriin, oleandrin, cardenolides, and odoroside. Additionally, this plant species produces secondary metabolites with medicinal uses, including steroids, flavonoids, and alkaloids. Antibacterial, anthelmintic, anti-inflammatory, hepatoprotective, immunopotential, anti-pyretic, antioxidant, antifungal, anticancer, and anti-HIV activity are among the significant pharmacological activities. Nerium indicum is also highly well-liked for its traditional medical applications, which include treating inflammation, wound healing, cancer, asthma, corns, heart disease, and epilepsy. Its bloom is the source of a green dye that is used to cure skin conditions, promote wound healing, and have anti-inflammatory properties. Both ultrasonic transesterification and the magnetic stirrer method have been utilized to produce biodiesel from nerium oleander oil. When administered topically, Nerium oleander's special qualities also have a notable age-defying effect. Nerium oleander to acquire several C and N compounds as well as heavy metals that are frequently produced by cars, including as Pb, Cd, Ni, and Zn. Based on the significance of nerium, the study was conducted in the Kanyakumari district of Tamil Nadu, where there is a greater area dedicated to nerium plant cultivation. The study's focus was on the factors that influence nerium cultivation, the factors that contribute to the volatility of nerium prices, and the challenges that farmers face in terms of production and marketing.

Machine learning approaches in designing anti-HIV nitroimidazoles: 2D/3D QSAR, kNN-MFA, docking, dynamics, PCA analysis and MMGBSA studies

In this study, newly synthesized 20 nitroimidazole derivatives were subjected to 2D and 3D Quantitative Structure-Activity Relationship (QSAR) study to investigate their anti-HIV activity against both ROD and IIIB strains. Later, proposed hypothesis was virtually proved by further in-silico studies. In statistically significant 2D-QSAR models r2 values for IIIB strains 0.9241 and for ROD strains 0.9412 with corresponding q2 values of 0.7706 and 0.8299, were obtained, respectively. Different models were constructed using three different kNN-MFA 3D QSAR approaches such as SW-FB, SA score, and GA. By using the generated hypothesis, newer analogues of nitroimidazole derivatives was designed and molecular modelling studies were conducted to prove the hypothesis. The three molecules were displayed the good docking scores compared to the reference molecule. The stabilities of docked complexes were analyzed by MD simulations and MMGB/SA calculations. These results offer insightful design guidance for novel anti-HIV compounds synthesis and suggest interesting directions for future pharmaceutical research.

Cinnamon an all-Inclusive Review: Detailed Examination of the Botanical Characteristics, Pharmacological properties, and Therapeutic Potential of Diverse Cinnamon Species

Cinnamomum is a genus belonging to the Lauraceae family and has been traditionally used for medicinal and culinary purposes. Southern India and Sri Lanka are the native habitats of the Cinnamomum genus. The two most significant types of cinnamon are Ceylon and cassia, this can be bought on marketplaces in both Europe and the US. Cinnamon is rich in phytochemicals such asPhyto alkaloids, Bioflavonoids, proteins, glycosides, phenols, terpenoids, tannins, and carbohydrates. The most significant components of cinnamon are cinnamaldehyde, cinnamate and cinnamic acid which are found in the essential oil and contribute to the aroma and numerous biological properties associated with cinnamon. Cinnamon is used in a variety of goods, including traditional spices, incense, fragrances, and food. It is also used in Ayurvedic medicine to regulate the Vata and Pitta elements in the body. It's been discovered that cinnamon possesses anti-diabetic, antibacterial, antioxidant, anti-inflammatory, anticancer, anti-HIV activity, wound healing, and anti-anxiety and depression properties. This review article offers comprehensive insights into theplant morphology, ancestral uses, chemical constituents with their pharmacological actions of various species of cinnamon as medicine.

Exploring American Elderberry Compounds for Antioxidant, Antiviral, and Antibacterial Properties Through High-Throughput Screening Assays Combined with Untargeted Metabolomics.

American elderberry (Sambucus nigra subsp. canadensis) is a rapidly emerging new perennial crop for Missouri, recognized for its high level of bioactive compounds with significant health benefits, including antibacterial, antiviral, and antioxidant properties. A high-throughput screening assay combined with untargeted metabolomics analysis was utilized on American elderberry juice from 21 genotypes to explore and characterize these bioactive compounds. Our metabolomics study has identified 32 putative bioactive compounds in the American Elderberry juices. An array of high-throughput screening bioassays was conducted to evaluate 1) total antioxidant capacity, 2) activation of antioxidant response elements (ARE), 3) antiviral activity, and 4) antibacterial activity of the putatively identified compounds. Our results revealed that 14 of the 32 American elderberry compounds exhibited strong antioxidant activity. Four compounds (isorhamnetin 3-O-glucoside, kaempferol, quercetin, and naringenin) activated ARE activity and were found to be non-cytotoxic to cells. Notably, six of the 32 compounds demonstrated significant antiviral activity in an in vitro TZM-bl assay against two strains of HIV-1 virus, CXCR4-dependent NL4-3 virus and CCR5-dependent BaL virus. Luteolin showed the most potent anti-HIV activity against the NL4-3 virus (IC50 = 1.49 μM), followed by isorhamnetin (IC50 = 1.67 μM). The most potent anti-HIV compound against the BaL virus was myricetin (IC50 = 1.14 μM), followed by luteolin (IC50 = 4.38 μM). Additionally, six compounds were found to have antibacterial activity against gram-positive bacteria S. aureus, with cyanidin 3-O-rutinoside having the most potent antibacterial activity in vitro (IC50 = 2.9 μM), followed by cyanidin 3-O-glucoside (IC50 = 3.7 μM). These findings support and validate the potential health benefits of compounds found in American elderberry juices and highlight their potential for use in dietary supplements as well as innovative applications in health and medicine.

Exploring the role of topological descriptors to predict physicochemical properties of anti-HIV drugs by using supervised machine learning algorithms

In order to explore the role of topological indices for predicting physio-chemical properties of anti-HIV drugs, this research uses python program-based algorithms to compute topological indices as well as machine learning algorithms. Degree-based topological indices are calculated using Python algorithm, providing important information about the structural behavior of drugs that are essential to their anti-HIV effectiveness. Furthermore, machine learning algorithms analyze the physio-chemical properties that correspond to anti-HIV activities, making use of their ability to identify complex trends in large, convoluted datasets. In addition to improving our comprehension of the links between molecular structure and effectiveness, the collaboration between machine learning and QSPR research further highlights the potential of computational approaches in drug discovery. This work reveals the mechanisms underlying anti-HIV effectiveness, which paves the way for the development of more potent anti-HIV drugs. This work reveals the mechanisms underlying anti-HIV efficiency, which paves the way for the development of more potent anti-HIV drugs which demonstrates the invaluable advantages of machine learning in assessing drug properties by clarifying the biological processes underlying anti-HIV behavior, which paves the way for the design and development of more effective anti-HIV drugs.

An Overview on the Synthesis of Lamellarins and Related Compounds with Biological Interest.

Lamellarins are natural products with a [3,4]-fused pyrrolocoumarin skeleton possessing interesting biological properties. More than 70 members have been isolated from diverse marine organisms, such as sponges, ascidians, mollusks, and tunicates. There is a continuous interest in the synthesis of these compounds. In this review, the synthetic strategies for the synthesis of the title compounds are presented along with their biological properties. Three routes are followed for the synthesis of lamellarins. Initially, pyrrole derivatives are the starting or intermediate compounds, and then they are fused to isoquinoline or a coumarin moiety. Second, isoquinoline is the starting compound fused to an indole moiety. In the last route, coumarins are the starting compounds, which are fused to a pyrrole moiety and an isoquinoline scaffold. The synthesis of isolamellarins, azacoumestans, isoazacoumestans, and analogues is also described. The above synthesis is achieved via metal-catalyzed cross-coupling, [3 + 2] cycloaddition, substitution, and lactonization reactions. The title compounds exhibit cytotoxic, multidrug resistance (MDR), topoisomerase I-targeted antitumor, anti-HIV, antiproliferative, anti-neurodegenerative disease, and anti-inflammatory activities.

Design, synthesis, molecular dynamics studies and biological evaluations of 4-hydroxy-5-pyrrolinone-3-carbohydrazides as HIV-1 integrase inhibitors

Acquired immune deficiency syndrome (AIDS) diseases despite the efficacy of anti-HIV therapy, remain one of the human's most serious problems. Hence, the introduction of novel anti-HIV agents as first-line therapy is still required. HIV integrase lacking human enzyme homologous is an interesting target for developing new anti-HIV drugs. Following our attempts to describe active integrase inhibitor structures, here a series of novel 4-Hydroxy-5-pyrrolinone-3-carbohydrazides as HIV integrase inhibitor agents were identified. Biological results showed that all compounds could inhibit integrase strand transfer reaction and also exhibited anti-HIV activity in a cell-based assay. The interaction between integrase and designed compounds was investigated using molecular docking and molecular dynamics simulations.

Potential anti-HIV and antitrypanosomal components revealed in Sorindeia nitidula via LC-ESI-QTOF-MS/MS

Sorindeia nitidula (Anacardiaceae) is used by traditional practitioners to treat influenza illnesses with cephalgia and febrile aches. However, the potential active ingredients for its remarkable antioxidant, anti-HIV and antitrypanosomal activities remain unexplored. The present study aims to evaluate the antioxidant, anti-HIV and antitrypanosomal activities of the ethyl acetate extract of S. nitidula (SN) in order to screen out the bioactive compounds and to analyze their possible mechanisms of action. Overall, 21 phenolic compounds were annotated, by using the MS and MS/MS information provided by the QTOF-MS. In vitro assays on the extract revealed potent antioxidant (IC50 = 0.0129 ± 0.0001 mg/mL), anti-HIV (IC50 = 1.736 ± 0.036 µM), antitrypanosomal (IC50 = 1.040 ± 0.010 µM) activities. Furthermore, SN did not present cytotoxic effect on HeLa cancer cell lines. The integrated strategy based on LC-ESI-QTOF-MS/MS provided a powerful tool and a multidimensional perspective for further exploration of active ingredients in S. nitidula responsible for the antioxidant, anti-HIV and antitrypanosomal activities.

Maca (Lepidium meyenii Walp.) inhibits HIV-1 infection through the activity of thiadiazole alkaloids in viral integration

Ethnopharmacology relevanceLepidium meyenii Walp. (maca) has been traditionally used for centuries in the Central Andes region both as food and as medicine. In the last decades, its fertility enhancer properties have gained importance, with the majority of the scientific literature related to this topic. However, other traditional uses are less known as metabolic or infectious diseases. Aim of the studyThe main purpose of this study is to investigate the anti-infectious activity of L. meyenii, specifically in HIV-1 infection. There are previous reports of the transcriptional related activity of L. meyenii extracts in human T lymphocytes via transcription factors as NF-κB. Since T lymphocytes are the main target of HIV-1 infection and NF-κB is strongly involved in HIV-1 transcription, L. meyenii could display antiviral activity. Material and methodsChromatography and spectroscopy techniques were used to isolate and identify the compounds in the active extracts. An antiviral assay system based on recombinant viruses was used to evaluate the anti-HIV activity. Cell toxicity was tested for all the extracts and compounds. Viral entry was studied using VSV-HIV chimera viruses and reverse transcription and viral integration were studied by qPCR of viral DNA in infected cells. Finally, viral transcription was studied in primary lymphocytes transfected with HIV-1 or NF-κB luciferase reporter plasmids. Resultsn-Hexane extracts of purple maca displayed anti-HIV activity in an in vitro assay. A bioassay-guided fractionation led to the identification of three thiadiazole alkaloids with antiviral activity. All the compounds were able to inhibit HIV infection of MT-2 cell lines and primary lymphocytes (PBMCs) with IC50 values in the low micromolar range. The mechanism of action differs between the three compounds: one of them showed activity on viral entry, and all the three compounds inhibited viral integration at low concentrations. Remarkably, none of the compounds inhibited reverse transcription or viral transcription. Conclusionsn-Hexane extracts of the purple ecotype of L. meyenii inhibit HIV-1 infection in vitro and three active thiadiazole alkaloids were isolated acting mainly on viral integration and viral entry.

Effect of progestin-based contraceptives on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls. Fifty-nine sexually active, HIV-uninfected girls aged 15-19, were recruited from the Washington DC metro area and self-selected into Control (condoms only), combined oral contraceptive pills, LNG-IUD, ETNG and DMPA groups. Vaginal swabs were collected at baseline prior to contraceptive use and at 3-month follow-up visit. Vaginal secretions were tested for pro-inflammatory (IL-1α, IL-1β, TNF-α, IL-6, IL-8, MIP-3α, IP-10, RANTES, MIP-1α, MIP-1β) and anti-inflammatory/anti-HIV (Serpin-A1, Elafin, Beta-Defensin-2, SLPI) immune biomarkers using ELISA and for anti-HIV activity using TZM-bl assay. Vaginal microbiome was evaluated using 16S rRNA gene sequencing. Data were analyzed using SAS Version 9. Among the 34 participants who completed both visits, no significant changes in median biomarker concentrations, HIV inhibition and microbiome composition were observed between baseline and follow-up visits for any of the contraceptive groups. IL-8 (p<0.01), MIP-3α (0.02), Elafin (p = 0.03) and RANTES (p<0.01) differed significantly by race whereas IL-6 was significantly different by age (p = 0.03). We conclude that 3-month use of LNG-IUD, ETNG and DMPA have minimal effects on adolescent vaginal immune microenvironment, and therefore unlikely to impact HIV risk. Future studies with larger sample size and longer follow-up are recommended to continue to evaluate effects of contraceptives on the lower genital tract immunity and susceptibility to sexually transmitted infections.

A computational approach to evaluate caffeoylquinic acids and flavonoids in Pluchea indica Less. leaves as potential anti-HIV agents

Context: The attachment of human immunodeficiency virus type 1 glycoprotein 120 (HIV-1 gp120) to the CD4 receptor of human immune cells is the beginning of HIV-1 infection. Stimulation of reactive oxygen species (ROS) production through upregulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX-2) and -4 (NOX-4), and cytochrome P450 2E1 (CYP2E1) of the virus can be a potential target for anti-HIV agents. Aims: To evaluate the inhibitory effects of caffeoylquinic acids (CQAs) and flavonoids of Pluchea indica leaves against the binding of HIV-1 gp120 with CD4 receptor and their antioxidant activities via interactions with NOX-2, NOX-4, and CYP2E1 through in silico study. Methods: Ten CQAs and nine flavonoids of P. indica were docked to the 3TGS (gp120 HIV-1), 2CDU (NOX-2), 3A1F (NOX-4), and 3T3Z (CYP2E1) receptors using the AutoDockTools 1.5.7. Physicochemical and pharmacokinetics properties were predicted using the pkCSM online tool, while toxicity was predicted using the ProTox-II webserver. Results: Mostly, all of the CQAs and flavonoids were able to bind to all receptors. 3,4-Di-O-caffeoylquinic acid has the lowest binding energy (-8.79 kcal/mol) against 3TGS (gp120). 5-O-Caffeoylquinic acid and apigenin have great potential as antioxidants due to their good binding with NOX-2 and CYP2E1. However, CQAs might have ADME problems. Most test compounds did not cause hepatotoxicity, carcinogenicity, or mutagenicity. All test compounds have no cytotoxic potential. However, all CQAs have the potential to be immunotoxins. Conclusions: The findings indicated that 3,4-di-O-caffeylquinic acid could be a potential inhibitor of HIV-1 gp120-CD4 binding, while 5-O-caffeoylquinic acid and apigenin demonstrated strong antioxidant activities via NOX-2 and CYP2E1 inhibition. However, in-depth studies, including experimental in vitro and in vivo studies, are required to validate the anti-HIV activity of the compounds further.

Synthesis, characterisation, DFT and biological evaluation of 4-(1-ethylbenzimidazol-2-yl)-2-(arylamino)thiazoles

The compounds 4-(1-ethylbenzimidazol-2-yl)-2-(arylamino)thiazoles were expected to have many biological activities and were synthesized from 1,2-diaminobenzene and lactic acid. The synthesized compounds are characterised by FT-IR, 1H NMR and mass spectroscopy. Thiazole moiety present in the compounds was found to possess anticancer, anti-HIV activities. Theoretical information on the optimized geometry, vibrational frequencies and atomic charges in the ground state were determined by means of density functional theory (DFT) using standard B3LYP/6-31G basis set with Gaussian ’09 software. Mulliken population analysis was performed on the atomic charges and the HOMO-LUMO energies were calculated. From the HOMO-LUMO energy gap, we know that the charge transfer occurs within the molecule. Docking studies are also done by using PyRx and are visualized by PyMoL software. By 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method, anti-oxidant activity of the synthesized compounds was evaluated. In vitro cytotoxic activity of the compounds against A549 cell lines was evaluated by MTT assay.

Exploring the therapeutic potential of silver nanocomposition of Catharanthus roseus leaves extract for antimicrobial and antiviral activities: A pilot study

Silver nanoparticles (AgNPs) synthesized from natural sources offer promising solutions for combating microbial and viral infections. Catharanthus roseus (Periwinkle), renowned for its diverse pharmacological properties, provides a sustainable and eco-friendly method for producing AgNPs with significant antimicrobial and antiviral effects. This study explores the cytotoxic potential of AgNPs derived from C. roseus and their antibacterial, antifungal, and anti-HIV activities, highlighting the novelty of employing a green synthesis approach. AgNPs from C. roseus leaf extract (AgNP-CR) were synthesized and characterized using spectroscopic and microscopic techniques to determine their physicochemical properties. The antibacterial activity of AgNP-CR was assessed against clinically relevant bacterial strains, and antifungal activity was evaluated against common fungal pathogens. Additionally, anti-HIV activity was investigated through in vitro assays using HIV-infected cells. Results demonstrated significant antibacterial activity of AgNP-CR against both gram-positive and gram-negative bacteria. Furthermore, AgNP-CR exhibited antifungal activity against pathogenic Aspergillus species. Importantly, AgNP-CR showed promising anti-HIV activity by inhibiting viral replication and cytopathic effects in infected cells. Cytotoxicity assays were also conducted to ensure the safety profile of the nanoparticles. Overall, this pilot study underscores the therapeutic potential of AgNPs synthesized from C. roseus in addressing bacterial, fungal, and viral infections. Further research is warranted to elucidate their mechanisms of action and optimize formulations for clinical applications.

Light promotes pharmacological activities of bitter gourd (Momordica charantia) via McHY5/McHY5-X1 and McPIF1-X1/McPIF3 antagonistic regulation in MAP30 transcription

MAP30, a ribosome-inactivating protein mainly isolated from the fruits and seeds of bitter gourd (Momordica charantia), has many pharmacological properties, such as anti-HIV and anti-tumor activities. Using qPCR analysis, we found that MAP30 transcription was higher in light, but drastically reduced in darkness. However, the molecular mechanism by which MAP30 is regulated remains unclear. Using yeast one-hybrid (Y1H) library screening, we found that McHY5, a homolog of AtHY5, bound to the MAP30 promoter. In addition, McHY5 and its homolog McHY5-X1 are identified as positive regulators binding to the MAP30 promoter by using Y1H, Electrophoretic mobility shift assay (EMSA) and Dual-Luciferase Reporter (DLR) assay. Due to MAP30 is not present in Arabidopsis we transformed pMAP30:MAP30 to Col and obtained transgenic line 18. Compared with pMAP30:MAP30/Col 18#, MAP30 transcription was largely reduced in pMAP30:MAP30 18#/Athy5–215 whether under light or dark conditions. Moreover, approximately 70 % of the tested bitter gourd germplasms showed consistent expression patterns of McHY5/McHY5-X1 and MAP30 under light conditions. In contrast to McHY5, McPIF1-X1 and McPIF3 acted as inactivators to inhibit MAP30 transcription. In this study, we found that MAP30 transcription was activated by McHY5 and McHY5-X1 in light, while McPIF1-X1 and McPIF3 inhibited MAP30 transcription mainly in darkness. Conclusively, we established the antagonistic module of McHY5/McHY5-X1 and McPIF1-X1/McPIF3 in MAP30 transcription regulation. This work expands our understanding of the regulatory mechanism of MAP30 and provides a valuable conceptual guidance for cultivating high pharmacological activity bitter gourd varieties with high MAP30 protein levels.

Coumarin/β-Cyclodextrin Inclusion Complexes Promote Acceleration and Improvement of Wound Healing.

Coumarins have great pharmacotherapeutic potential, presenting several biological and pharmaceutical applications, like antibiotic, fungicidal, anti-inflammatory, anticancer, anti-HIV, and healing activities, among others. These molecules are practically insoluble in water, and for biological applications, it became necessary to complex them with cyclodextrins (CDs), which influence their bioavailability in the target organism. In this work, we studied two coumarins, and it was possible to conclude that there were structural differences between 4,7-dimethyl-2H-chromen-2-one (DMC) and 7-methoxy-4-methyl-2H-chromen-2-one (MMC)/β-CD that were solubilized in ethanol, frozen, and lyophilized (FL) and the mechanical mixtures (MM). In addition, the inclusion complex formation improved the solubility of DMC and MMC in an aqueous medium. According to the data, the inclusion complexes were formed and are more stable at a molar ratio of 2:1 coumarin/β-CD, and hydrogen bonds along with π-π stacking interactions are responsible for the better stability, especially for (MMC)2@β-CD. In vivo wound healing studies in mice showed faster re-epithelialization and the best deposition of collagen with the (DMC)2@β-CD (FL) and (MMC)2@β-CD (FL) inclusion complexes, demonstrating clearly that they have potential in wound repair. Therefore, (DMC)2@β-CD (FL) deserves great attention because it presented excellent results, reducing the granulation tissue and mast cell density and improving collagen remodeling. Finally, the protein binding studies suggested that the anti-inflammatory activities might exert their biological function through the inhibition of MEK, providing the possibility of development of new MEK inhibitors.

Anti-HIV Activity and Immunomodulatory Properties of Fractionated Crude Extracts of Alternaria alternata.

Developing new anti-human immunodeficiency virus (HIV) drug candidates that target different sites in HIV-1 replication, with better resistance profiles and lower drug toxicity, is essential to eradicating HIV. This study investigated the potential of fractionated crude extracts of Alternaria alternata as immunomodulatory or anti-HIV drug candidates. Solid-phase extraction (SPE) was used to fractionate A. alternata PO4PR2 using three different columns: MAX (Mixed-mode, strong Anion-eXchange), MCX (Mixed-mode, strong Cation-eXchange), and HLB (Hydrophilic-Lipophilic Balance) with methanol gradient methods (5%, 45%, and 95%). An MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to assess the cell viability and cytotoxicity of the fractionated crude extract A. alternata PO4PR2 in the TZM-bl cell lines. This was followed by a luciferase-based antiviral assay to assess the antiviral activity of A. alternata PO4PR2. A time of addition (TOA) assay was performed to ascertain the mechanism of inhibition employed by the fractionated crude extract of A. alternata PO4PR2 in the HIV life cycle. The p24 titer was determined using an ELISA, while a luciferase-based antiviral assay was used to evaluate the HIV percentage inhibition for different HIV-1 replication cycles. The TOA assay was established using antiviral drugs that target different sites in the HIV replication cycle. These included maraviroc, azidothymidine, raltegravir, and amprenavir. The immunomodulatory effect of the fractionated crude extracts on CD4+ T cells was measured by a flow cytometric analysis, for which fluorochrome-labelled monoclonal antibodies were used as markers for activation (CD38 and HLA-DR) and exhaustion (PD-1). The MCX fraction demonstrated a more significant anti-HIV inhibition than that of the fractions generated in other columns, with an IC50 of 0.3619 µg/mL, an HIV inhibition of 77%, 5% HLB (IC50: 0.7232 µg/mL; HIV inhibition of 64%), and 5% MAX (IC50: 5.240 µg/mL; HIV inhibition of 67%). It was evident from the time of addition data that the crude extract and the 5% MCX fraction inhibited viral binding (68%), reverse transcription (75%), integration (98%), and proteolysis (77%). It was shown that A. alternata (the MCX fraction) have a significant inhibitory effect on reverse transcription (75% HIV inhibition) and integration (100% HIV inhibition). The 5% MCX (p = 0.0062), 5% HLB (p = 0.0269), and 5% MAX (p = 0.0117) fractionated A. alternata crude extracts had low levels of CD4+ T cell (CD38 + HLA-DR+) activation compared to those of the AZT treatment, while CD4+ T cell activation was insignificant. The 5% MAX and HLB A. alternata fractions may possess immunomodulatory compounds with less anti-HIV-1 activity. A. alternata could be a key source of innovative anti-HIV drugs with immunomodulatory characteristics.

Green Approach Toward Triazole Forming Reactions for Developing Anticancer Drugs.

Compounds containing triazole have many significant applications in the dye and ink industry, corrosion inhibitors, polymers, and pharmaceutical industries. These compounds possess many antimicrobial, antioxidant, anticancer, antiviral, anti-HIV, antitubercular, and anticancer activities. Several synthetic methods have been reported for reducing time, minimizing synthetic steps, and utilizing less hazardous and toxic solvents and reagents to improve the yield of triazoles and their analogues synthesis. Among the improvement in methods, green approaches towards triazole forming biologically active compounds, especially anticancer compounds, would be very important for pharmaceutical industries as well as global research community. In this article, we have reviewed the last five years of green chemistry approaches on click reaction between alkyl azide and alkynes to install 1,2,3-triazole moiety in natural products and synthetic drug-like molecules, such as in colchicine, flavanone cardanol, bisphosphonates, thiabendazoles, piperazine, prostanoid, flavonoid, quinoxalines, C-azanucleoside, dibenzylamine, and aryl-azotriazole. The cytotoxicity of triazole hybrid analogues was evaluated against a panel of cancer cell lines, including multidrug-resistant cell lines.

Daphnane diterpenoid orthoesters with an odd-numbered aliphatic side chain from Daphne pedunculata.

Daphnane diterpenoids were recognized for their extensive range of potent biological activities. In the present study, phytochemical investigation including LC-MS/MS analysis resulted in the identification of five daphnane diterpenoid orthoesters (1-5). Among the five daphnane diterpenoids, two previously unreported compounds, daphnepedunins I and J (2 and 4) were isolated from Daphne pedunculata. The structure of new compounds was elucidated with extensive physicochemical and spectroscopic analyses. Their structure was characterized by the presence of an unusual odd-numbered aliphatic chain connected to an orthoester. The isolated compounds were evaluated for their anti-HIV activity against HIV-1 infection of MT4 cells, and the results indicated that compound 1 showed the most potent anti-HIV activity with an IC50 value of 0.82nM.