anti-HIV Properties Research Articles

Advances in Isatin-derived Compounds for Modern Cancer Therapy: A Comprehensive Review

Isatin has garnered significant interest due to its wide range of pharmacological activities, including anti-inflammatory, anti-HIV, anticancer, antioxidant, antimicrobial, and antifungal properties. As a natural compound found in both humans (as a metabolic derivative of adrenaline) and plants (melastatin), its unique structure, with carbonyl groups at positions 2 and 3 and an NH group at position 1, makes it a valuable scaffold for designing bioactive analogs. Researchers have employed various strategies to enhance these analogs' pharmacological properties, with studies consistently highlighting their multitarget potential. This review focuses on isatin derivatives in medicinal chemistry, particularly as chemotherapeutic agents, and outlines common synthetic methods and recent advances in their biological and therapeutic applications. Notably, substitution at the C-5 position with electron-donating groups (EDGs) has shown strong antitumor activity against HepG2 cells (IC50 = 6.99 μM), approaching the efficacy of doxorubicin (IC50 = 3.56 μM). Modifications at the C-3 carbonyl group have also demonstrated 300-fold increased potency at 0.03 μM against Jurkat T lymphocytes. Structural variations within the isatin scaffold have shown significant cytotoxicity across several cancer cell lines, underscoring their potential in anticancer drug development.

A Brief Review-an Update on 1,3,4-Oxadiazole

Abstract: The 1,3,4-oxadiazole nucleus is a biologically necessary scaffold that exhibits a wide range of pharmacological activities. The broad and strong activity of 1,3,4-oxadiazole and their derivatives has established them as significant pharmacological scaffolds, particularly in the treatment of cancer disease. A number of di-, tri-, aromatic, and heterocyclic substituted 1,3,4- oxadiazole derivatives have been reported to possess potent biological activities; these substituted 1,3,4-oxadiazoles had different mechanisms of action and contributed to the development of biologically active drugs. This review is intended to supplement previous reviews by reviewing the literature on the different activities of 1,3,4-oxadiazole derivatives from the last fifteen years. 1,3,4-oxadiazole can be produced in a number of ways and has a wide range of possible pharmacological uses. As a result, scientists have created novel procedures for the production of 1,3,4- oxadiazole derivatives and their use in medicine presently. Anticancer, antibacterial, antiinflammatory, anti-HIV, anti-tubercular, anti-diabetic, antifungal, and other properties are among the activities. In this review, we discussed various research works based on 1,3,4-oxadiazole derivatives synthetic procedure and assessment of different biological activities. Many researchers may find the material on this page helpful, which could lead to the discovery of new medicinal species for society.

Anti-diabetic, Anti-cancer Potential and Anti HIV of Bitter Gourd (Momordica charantia) Extract: A Mini Review

Aims: To review the antidiabetic properties, pharmacological characteristics, and phytochemical research on Momordica Ccharantia (bitter gourd) and assess its potential as a therapeutic agent for diabetes and cancer prevention. Study Design: Review of existing literature and research studies, including pre-clinical trials and animal and in vitro studies. Methodology: Analysis of traditional uses, pharmacological data, and phytochemical research on M. Charantia. Evaluation of anti-diabetic and anti-HIV properties based on available studies. Results: Charantia has shown anti-diabetic and hypoglycemic effects in pre-clinical studies. Limited and unreliable clinical data due to poor research design and inadequate statistical power. Recent studies indicate potential anti-tumor, anti-diabetic, and anti-HIV properties. Plant extract components have demonstrated effectiveness in cancer prevention through immune function enhancement, induction of cell death, and inhibition of cancer-related processes. Conclusion: M. Charantia holds promise as a therapeutic agent for diabetes management and cancer prevention. However, there is a need for better-designed clinical trials to confirm its efficacy and establish reliable clinical evidence.

Identification of naturally occurring flavonoids as anticancer agents: In silico studies

It is recognized that flavonoids have a variety of functions in nature, including anti-inflammatory, antibacterial, antioxidant, anticancer, anti-HIV and neuroprotective properties. In the present study, molecular docking experiment was performed on 15 naturally occurring flavonoids as anticancer agents. The analysis of results was performed on the basis of docking score, glide energy and interaction with amino acids. Each flavonoid showed a specific interaction with target protein. Naringin showed interactions with amino acids GLN131, ASP145, PHE80, VAL83, GLU8, ILE10, THR89 (docking score −12.48) involved with the protein PDB ID: 1gij (inhibitor of cyclin-dependent kinase 4). Naringin further showed interactions with THR887, THR886, LYS833, ASP836 amino acids (docking score −15.078) involved with PDB ID: 5jhb (inhibitor of PI3K and tubulin). Orientin showed interactions with amino acids ASN150, ASP163, LYS43, VAL101 (docking score −13.89) with PDB ID: 2euf as inhibitor of cyclin-dependent kinase 6. Quercetin showed interactions with amino acids PHE1047, LEU840, CYS919, GLU917 (docking score −11.7) with PDB ID: 4agd as inhibitor of VEGF receptor tyrosine kinase inhibitor. Epigallocatechin gallate showed interactions with amino acids LYS868, GLU885, THR916, ASP1046 using protein PDB ID: 3ewh (docking score −10.004) as inhibitor of Tie-2 kinase. The given flavonoid drugs interaction with cancer targets shows their possible potential against various forms of cancer. Epigallocatechin gallate when docked with 3ewh showed best docking score with important interaction required for anticancer activity. In molecular dynamic study, Epigallocatechin gallate in complex with VEGFR2 kinase protein (PDB ID: 3ewh) with RMSD indicates the protein remained stable through the simulation of 100ns with fluctuation in the range of 1.5–3.5 Å. The provided docking results may be useful for the development of novel drug candidate for anticancer targets.

Phytochemical composition of Lagenaria siceraria fruits from KwaZulu-Natal and Limpopo, South Africa

Lagenaria siceraria (Molina) Standley is a food and medicinal source with anti-proliferative, anti-fertility, anti-HIV and anti-cancerous properties. The current study investigated the phytochemical constituents of L. siceraria fruits using gas chromatography/mass spectrometry (GC–MS). Five isoprenoids present in all investigated landraces were 1-Dodecene, 2,3-Dimethyldodecane, E-15-Heptadecenal, Eicosane, and Tridecane, 6-propyl. Lighter metabolites such as 1-Dodecene and 2,3-Dimethyldodecane were recorded at a shorter retention time range of 9.08–16.29 min over a lower relative peak area ranging from 1.09 to 6.97%. However, heavier compounds (E-15-Heptadecenal, Eicosane and Tridecane, 6-propyl) had a longer retention time range of 13.42–18.00 mins over a higher relative peak area range of 2.25–11.41%. Cluster analysis grouped landraces into 5 clusters (I -V) according to their fruit and seed attributes, and isoprenoid units significant to each cluster. Terpenoids were the prominent phytochemicals present in fruits. This is the most comprehensive study on the fruit phytochemical constituents of different L. siceraria landraces to date.

Synthesis, crystal structure, Hirshfeld surface analysis, computational investigations and molecular docking studies of (Z)-3-N-(methyl)-2-N’-(4-methoxyphenylimino) thiazolidin-4-one dihydrate

Thiazolidinones, widely utilized as a framework for synthesizing diverse molecules, demonstrate pharmacological activity and contribute to the creation of compounds with various biological effects, including antimicrobial, analgesic, antitumor, anti-inflammatory, anti-HIV, and antitubercular properties. The primary objective of this study was to develop a novel organic heterocyclic compound. Researchers successfully achieved this goal by synthesizing (Z)-2-((4-methoxycyclohexa-2,5‑dien-1-yl) imino)-3-methyl thiazolidin-4-one dihydrate (ZMThD), and the structural features of this newly synthesized compound were determined using single crystal X-ray diffraction (XRD). The compound crystallized in the orthorhombic system's P212121 space group. A notable feature of the structure is the precisely measured dihedral angle of 45.0° between the benzene and thiazolidinone rings, indicating a lack of π-π stacking and confirming the non-planar nature of the structure.To further support and elucidate the experimental findings, density functional theory (DFT) calculations were conducted using the B3LYP functional in conjunction with a 6–311 G (d, p) basis set. The optimized geometry results obtained from these calculations closely mirrored the experimental results. Additionally, the stability of the crystal structure was examined through Hirshfeld surface analysis and 2D fingerprint plots, revealing that H…H interactions (50.7%) and H…C/C…H interactions (24.3%) were the primary contributors to the intermolecular forces stabilizing the crystalline structure. The potent inhibitory activity of the screened compounds was rationalized through in-silico molecular modeling studies against the Insulin-degrading enzyme (IDE) enzyme. The compound exhibited a remarkable docking score of −6.8 Kcal/mole, characterized by hydrogen-bond and hydrophobic interactions.

Recent developments in catalytic and antimicrobial applications of benzimidazole Schiff base: A review

An amino acid and a carbonyl molecule are combined to generate Schiff bases complexes, which are useful compounds. Catalytic activity is high in many metals Schiff base complexes, especially chiral ones. Examples of processes include epoxidation, aldol condensation, hydroxylation, and oxidation. In several activities and in the presence of moisture, complexes display considerable catalytic activity. They have antibacterial, antifungal, antiviral, antimalarial, anticancer, and anti-HIV properties, among other biological activities. Research into these compounds’ coordination behavior has exploded because of specific metals on them, their biological activity and their intrinsic chemical interest as multidentate ligands. This article provides an overview of the numerous syntheses and uses for Schiff bases and their metal complexes.

Advances in chromone-based copper(ii) Schiff base complexes: synthesis, characterization, and versatile applications in pharmacology and biomimetic catalysis.

Chromones are well known as fundamental structural elements found in numerous natural compounds and medicinal substances. The Schiff bases of chromones have a much wider range of pharmacological applications such as antitumor, antioxidant, anti-HIV, antifungal, anti-inflammatory, and antimicrobial properties. A lot of research has been carried out on chromone-based copper(ii) Schiff-base complexes owing to their role in the organometallic domain and promise as potential bioactive cores. This review article is centered on copper(ii) Schiff-base complexes derived from chromones, highlighting their diverse range of pharmacological applications documented in the past decade, as well as the future research opportunities they offer.

Biological Potential of Ethyl Gallate

Most of the drugs have side effects in patients due to drug induced toxicity. The drug induced toxicity has to be reduced by addition of antioxidants which are available naturally. For example, ethyl gallate is one of the promising agents which has great antioxidant properties. Apart from antioxidant properties, it has anti-cancer, anti-inflammatory and anti-HIV properties. Combination dosing of drugs with ethyl gallate will reduce the drug induced toxicity by improving their actual potency. The motive of this review is to understand the importance of ethyl gallate showing antioxidant activity which when induced with a certain drug, decreases the toxic effects of drugs and has beneficial properties such as anti-inflammation and anti-HIV. The major benefit of ethyl gallate is that it is available in many natural products and can be obtained easily.

Multicomponent Synthesis Strategies, Catalytic Activities, and Potential Therapeutic Potential of Pyranocoumarins: A Comprehensive Review.

Fused coumarins, because of their remarkable biological and therapeutic properties, particularly pyranocoumarins, have caught the interest of synthetic organic chemists, leading to the development of more efficient and environmentally friendly protocols for synthesizing pyranocoumarin derivatives. These compounds are the most promising heterocycles discovered in both natural and synthetic sources, with anti-inflammatory, anti-HIV, antitubercular, antihyperglycemic, and antibacterial properties. This review employed the leading scientific databases Scopus, Web of Science, Google Scholar, and PubMed up to the end of 2022, as well as the combining terms pyranocoumarins, synthesis, isolation, structural elucidation, and biological activity. Among the catalysts employed, acidic magnetic nanocatalysts, transition metal catalysts, and carbon-based catalysts have all demonstrated improved reaction yields and facilitated reactions under milder conditions. Herein, the present review discusses the various multicomponent synthetic strategies for pyranocoumarins catalyzed by transition metal-based catalysts, transition metal-based nanocatalysts, transition metal-free catalysts, carbon-based nanocatalysts, and their potential pharmacological activities.

Ethnomedicinal Uses, Phytochemistry and Pharmacological Properties of Suregada Genus: A Review.

Plants of the Suregada Roxb. ex Rottler (formerly Gelonium Roxb. ex Willd) are utilized to treat various ailments, namely, hepatic, gum diseases, pyrexia, eczema, and venereal diseases. This review links the reported compounds to ethnomedicinal uses through pharmacological activities. The compounds possess anticancer, anti-allergic, antibacterial, anti-inflammatory, antioxidant, and anti-HIV properties. From the previous reports, 32 known species of the Suregada genus have been investigated morphologically, and nine were investigated for their phytochemistry and pharmacology. Phytochemistry, ethnomedicinal, and pharmacological uses of the other 23 Suregada species are not known and/or not reported. In this review, abietane diterpenoids are the main compounds expressed by the Suregada, accounting for 71 of the 114 reported compounds. Ten triterpenoids and sterols, one aliphatic, two lignans, five flavonoids, and twenty-one nitrogen-containing compounds have been reported from the genus.

Shikonin and Alkannin inhibit ATP synthase and impede the cell growth in Escherichia coli

Naturally occurring naphthoquinones, shikonin and alkannin, are important ingredients of traditional Chinese medicine Zicao. These constituents are reported to have many therapeutic uses, such as wound healing; scar treatment; and anti-inflammation, anti-acne, anti-ulcer, anti-HIV, anticancer, and antibacterial properties. The primary objective of this investigation was to explore the effect of shikonin and alkannin on Escherichia coli ATP synthase and its cell growth. Shikonin caused complete (100 %) inhibition, and alkannin caused partial (79 %) inhibition of wild-type E. coli ATP synthase. Both caused partial (4 %–27 %) inhibition of ATP synthase with genetically modified phytochemical binding site. The growth inhibition of strains expressing normal, deficient, and mutant ATP synthase by shikonin and alkannin, corroborated the inhibition observed in isolated normal wild-type and mutant ATP synthase. Trivial inhibition of mutant enzymes indicated αR283D, αE284R, βV265Q, and γT273A are essential for formation of the phytochemical binding site where shikonin and alkannin bind. Further, shikonin was a potent inhibitor of ATP synthase than alkannin. The antimicrobial properties of shikonin and alkannin were tied to the binding at phytochemical site of microbial ATP synthase. Selective targeting of bacterial ATP synthase by shikonin and alkannin may be an advantageous alternative to address the antibiotic resistance issue.

Copper-Promoted Intramolecular Oxidative Dehydrogenation for Synthesizing Dihydroisocoumarins and Isocoumarins.

Isocoumarins and dihydroisocoumarins are important skeletons with a wide range of biological activities, such as anti-bacterial, anti-allergy, anti-fungal, anti-tumor, and anti-HIV properties. Herein, we demonstrated divergent syntheses of isocoumarins and 3,4-dihydroisocoumarins by intramolecular dehydrogenative cyclization of 2-(3-oxobutyl) benzoic acids. This transformation undergoes Csp3-H bonds and O-H bonds coupling in air using copper salt. The reactions may undergo free radical process.

Sulforaphane prevents the reactivation of HIV-1 by suppressing NFκB signaling

Despite more than 20 years of combination antiretroviral therapy (cART), complete eradication of HIV remains a daunting task. While cART has been very effective in limiting new cycles of infection and keeping viral load below detectable levels with partial restoration of immune functions, it cannot provide a cure. Evidently, the interruption of cART leads to a quick rebound of the viral load within a few weeks. These consistent observations have revealed HIV ability to persist as an undetectable latent reservoir in a variety of tissues that remain insensitive to antiretroviral therapies. The ‘Block-and-Lock’ approach to drive latent cells into deep latency has emerged as a viable strategy to achieve a functional cure. It entails the development of latency-promoting agents with anti-HIV functions. Recent reports have suggested sulforaphane (SFN), an inducer of NRF-2 (nuclear erythroid 2-related factor 2)-mediated antioxidative signaling, to possess anti-HIV properties by restricting HIV replication at the early stages. However, the effect of SFN on the expression of integrated provirus remains unexplored. We have hypothesized that SFN may promote latency and prevent reactivation. Our results indicate that SFN can render latently infected monocytes and CD4+ T cells resistant to reactivation. SFN treatments antagonized the effects of known latency reactivating agents, tumor necrosis pactor (TNF-α), and phorbol 12-myristate 13-acetate (PMA), and caused a significant reduction in HIV transcription, viral RNA copies, and p24 levels. Furthermore, this block of reactivation was found to be mediated by SFN-induced NRF-2 signaling that specifically decreased the activation of NFκB signaling and thus restricted the HIV-1 promoter (5′LTR) activity. Overall, our study provides compelling evidence to highlight the latency-promoting potential of SFN which could be used in the ‘Block-and-Lock’ approach to achieve an HIV cure.

Computational Modeling, High-Level Soluble Expression and In Vitro Cytotoxicity Assessment of Recombinant Pseudomonas aeruginosa Azurin: A Promising Anti-Cancer Therapeutic Candidate.

Azurin is a natural protein produced by Pseudomonas aeruginosa that exhibits potential anti-tumor, anti-HIV, and anti-parasitic properties. The current study aimed to investigate the potential of azurin protein against breast cancer using both in silico and in vitro analyses. The amino acid sequence of Azurin was used to predict its secondary and tertiary structures, along with its physicochemical properties, using online software. The resulting structure was validated and confirmed using Ramachandran plots and ERRAT2. The mature azurin protein comprises 128 amino acids, and the top-ranked structure obtained from I-TASSER was shown to have a molecular weight of 14 kDa and a quality factor of 100% by ERRAT2, with 87.4% of residues in the favored region of the Ramachandran plot. Docking and simulation studies of azurin protein were conducted using HDOCK and Desmond servers, respectively. The resulting analysis revealed that Azurin docked against p53 and EphB2 receptors demonstrated maximum binding affinity, indicating its potential to cause apoptosis. The recombinant azurin gene was successfully cloned and expressed in a BL21 (DE3) strain using a pET20b expression vector under the control of the pelB ladder, followed by IPTG induction. The azurin protein was purified to high levels using affinity chromatography, yielding 70 mg/L. In vitro cytotoxicity assay was performed using MCF-7 cells, revealing the significant cytotoxicity of the azurin protein to be 105 µg/mL. These findings highlight the potential of azurin protein as an anticancer drug candidate.

Comparative Study on Synthesis and Biological, Pharmaceutical Applications of Aromatic Substituted Chalcones

Abstract: Chalcones(1, 3, diaryl-2-propen-1-ones) are prominent compounds and therefore, various procedures have been worked out for their synthesis. This review highlights the synthesis and pharmacological properties of chalcone derivatives. Chalcones are flavonoids that have been studied extensively for their medicinal and biological properties. These chalcone derivatives have shown important antimalarial, anticancer, antimicrobial, anti-inflammatory, antioxidant, antituberculosis, anticonvulsant, antileishmanial, and anti-HIV properties. The new structural classes of compounds may prove to be lead molecules and good candidates for future investigations.

DIVERSE PHARMACOLOGICAL POTENTIALS OF BETULA UTILIS: A CRITICAL REVIEW

Herbs have wide range of pharmacological activities including antibacterial, anti-inflammatory, anticancer, antioxidant, and anti-HIV gives them great potential as treatments for a wide variety of infectious disorders. The present review was emphasized on the evaluation of diverse pharmacological potentials of Betula utilis that have been confirmed by the researchers. Studies were analysed and extracted from the publications done at Scopus, PubMed, Web of Science, and other reputed journals. The bark of the betula utilis tree has antiseptic and carminative properties. Betula utilis, a common medicinal plant, is just one of the more than a thousand plant species known to contain significant pharmacological characteristics. Betula utilis belongs to Betulaceae family that can be found on the moraines around Bhojbasa in Uttarakhand, India, not far from the mouth of the Gangotri glacier. A moderate-sized tree that can reach heights of up to 20 metres. Bark has shown different chemical constituents i.e., acetylo-heanolic acid, lupeol, oleanolic acid, lupenone etc. Traditional use shows that bark has been used in treating a wide range of conditions, including bronchitis, convulsions, leprosy, blood disorders, contraceptive, antibacterial, fragrant, carminative, ear infections etc. It has been shown to have potent anticancer effects. Because to its many beneficial pharmacological properties, including antibacterial, anticancer, anti-obesity, antihyperglycemic, anti-inflammatory, antioxidant, and anti-HIV properties. In conclusion, Betula utilis is a promising research-oriented plant that might be effective in the cure and management of numerous medical conditions/ ailments through incorporating in different suitable dosage forms.

A review on the genus Calophyllum (Clusiaceae): a potential medicinal tree species

Calophyllum is the genus of evergreen tropical flowering plants in the Clusiaceae family. They are predominantly located in Asia with some of its genus distributed in the Pacific Islands, Americas, Australasia and Africa. Plants of the genus are well known for their chemical properties with lots of secondary metabolites such as triterpenes, flavonoids, coumarins and xanthones. Compounds from Calophyllum have been reported to have cytoprotective, anti-HIV, anti-secretory, cytotoxic, antinociceptive, molluscicidal and antimicrobial properties. Some of the plants in Calophyllum are used in folk medicine to treat conditions like peptic ulcers, tumours, inflammation, infections and pain. Calophyllum genus is important with respect to their ecological as well as their medicinal properties. But in India, some species located in Western Ghats are in vulnerable stage. Even so, there is no remarkable studies carried out about this genus. So, for a sustainable environment, we should focus on the conservation, restoration and rehabilitation of the genus that makes huge differences in their population. This article reviews the genus Calophyllum of Western Ghats as a potential medicinal tree species.

Recent advances in biological applications of mannich bases — An overview

Mannich bases are beta-amino ketone-carrying compounds that are the end products of the Mannich reaction. The Mannich reaction is essential in the synthesis of nitrogen-containing compounds. The Mannich reaction, a nucleophilic addition reaction that forms carbon-carbon bonds, is employed in the synthesis of numerous natural products, drugs and other compounds. There are several aminoalkyl chain bearing Mannich bases with high curative value, such as fluoxetine, atropine, ethacrynic acid, trihexyphenidyl, and many others. According to the literature, Mannich bases are highly reactive and have been demonstrated to have powerful anti-inflammatory, anticancer, antifilarial, antibacterial, antifungal, anticonvulsant, anthelmintic, antitubercular, analgesic, anti-HIV, antimalarial, antipsychotic, antiviral, antilipase activity and other properties. The primary source of, -α,β-unsaturated ketone, which can be produced by deaminating the hydrogen atom of the amine group, is responsible for the biological action of Mannich bases. However, a number of minor biological functions of Mannich bases have been reported, including their ability to control blood pressure or prevent platelet aggregation, their impact on parasites and ulcers, and their use as medications for mental health issues. Since there is a greater need for anticonvulsant pharmaceuticals, these anticonvulsant medications containing N-mannich base groups will exhibit an increase in lipophilic nature and hence have improved blood-brain barrier penetration. The overview concludes with a brief explanation of the potential of Mannich bases as inhibitors of various enzymes or ligands for various receptors.

The Antiviral Compound PSP Inhibits HIV-1 Entry via PKR-Dependent Activation in Monocytic Cells.

Actin depolymerization factor (ADF) cofilin-1 is a key cytoskeleton component that serves to lessen cortical actin. HIV-1 manipulates cofilin-1 regulation as a pre- and post-entry requisite. Disruption of ADF signaling is associated with denial of entry. The unfolded protein response (UPR) marker Inositol-Requiring Enzyme-1α (IRE1α) and interferon-induced protein (IFN-IP) double-stranded RNA- activated protein kinase (PKR) are reported to overlap with actin components. In our published findings, Coriolus versicolor bioactive extract polysaccharide peptide (PSP) has demonstrated anti-HIV replicative properties in THP1 monocytic cells. However, its involvement towards viral infectivity has not been elucidated before. In the present study, we examined the roles of PKR and IRE1α in cofilin-1 phosphorylation and its HIV-1 restrictive roles in THP1. HIV-1 p24 antigen was measured through infected supernatant to determine PSP's restrictive potential. Quantitative proteomics was performed to analyze cytoskeletal and UPR regulators. PKR, IRE1α, and cofilin-1 biomarkers were measured through immunoblots. Validation of key proteome markers was done through RT-qPCR. PKR/IRE1α inhibitors were used to validate viral entry and cofilin-1 phosphorylation through Western blots. Our findings show that PSP treatment before infection leads to an overall lower infectivity. Additionally, PKR and IRE1α show to be key regulators in cofilin-1 phosphorylation and viral restriction.