Pyrazole Containing Anti-HIV Agents: An Update

Background: Pyrazole scaffolds have gained importance in drug discovery and development for various pharmacological activities like antiviral, antifungal, anticancer, antidepressant, anti-inflammatory, antibacterial, etc. Additionally, the pyrazole moiety has shown potent anti-HIV activity as a core heterocycle or substituted heterocycles derivatives (mono, di, tri, tetra, and fused pyrazole derivatives). To assist the development of further potential anti-HIV agents containing pyrazole nucleus, here we have summarized pyrazole containing anti-HIV compounds that have been reported by researchers all over the world for the last two decades. Objective: The present review concentrates on an assortment of pyrazole containing compounds, particularly for potential therapeutic activity against HIV. Methods: Google Scholar, Pubmed, and SciFinder were searched databases with ‘‘pyrazol’’ keywords. Further, the year of publication and keywords ‘‘Anti-HIV’’ filter was applied to obtain relevant reported literature for anti-HIV agents containing pyrazole as a core or substituted derivatives. Results: This review article has shown the comprehensive compilation of 220 compounds containing pyrazole nucleus and possessing anti-HIV activity by sorting approximately 40 research articles from 2001 to date. 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-(1H-pyrazol-3-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (13), 3-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-fluoro-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxamide (31), 3-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-fluoro-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxamide (88), 3-cyanophenoxypyrazole derivative (130), and 4-(4-chlorophenyl)-5-(4-methyl-5-((4-nitrophenyl)diazenyl)thiazol-2-yl)-3-phenyl-5,6-dihydro-4H-pyrazolo[4,3-d]isoxazole (178) were the most potent mono-, di-, tri-, tetra-substituted, and fused pyrazole derivatives, respectively, which have shown potent anti-HIV activity among all the described derivatives as compared with standard anti-HIV drugs. Conclusion: This review article provides an overview of the potential therapeutic activity of pyrazole derivatives against HIV that will be helpful for designing pyrazole containing compounds for anti-HIV activity.

Therapeutic potential of indole derivatives as anti-HIV agents: A mini-review

: Acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), is one of the leading causes of human deaths. The advent of different anti-HIV drugs over different disease progress has made AIDS/HIV from a deadly infection to chronic and manageable disease. However, the development of multidrug-resistant viruses, together with the severe side effects of anti-HIV agents, compromised their efficacy and limited the treatment options. Indoles, the most common frameworks in the bioactive molecules, represent attractive scaffolds for the design and development of novel drugs. Indole derivatives are potential inhibitors of HIV enzymes such as reverse transcriptase, integrase and protease, and some indole-based agents like Delavirdine have already been applied in clinics or under clinical evaluations for the treatment of AIDS/HIV, revealing that indole moiety is a useful template for the development of anti-HIV agents. This review focuses on the recent advancement of indole derivatives including indole alkaloids, hybrids, and dimers with anti-HIV potential, covering articles published between 2010 and 2020. The chemical structures, structure-activity relationship and mechanisms of action are also discussed.

Antimicrobial Peptide, LL-37, And Its Potential As An Anti-HIV Agent

Human immunodeficiency virus (HIV) continues to have a profound global health impact. New infections continue at a high rate despite the development of prophylactic therapies, prompting the need for development of novel preventative approaches. Antimicrobial peptides (AMPs), such as LL-37, display broad microbicidal properties and have potential as anti-HIV agents. LL-37 has been studied for its anti-HIV activity and the limited data available suggest it can inhibit HIV infection in primary T cells as well as exert inhibitory effects on key HIV enzymes. Its immunomodulatory properties may both enhance and inhibit HIV replication. In addition, LL-37 has both 1) the ability to kill other sexually-transmitted pathogens and 2) spermicidal activity; thus, it is a good candidate for multipurpose prevention technology. Further investigation of its anti-HIV activity is warranted.

Pyrroles as Privileged Scaffolds in the Search for New Potential HIV Inhibitors

Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) and remains a global health problem four decades after the report of its first case. Despite success in viral load suppression and the increase in patient survival due to combined antiretroviral therapy (cART), the development of new drugs has become imperative due to strains that have become resistant to antiretrovirals. In this context, there has been a continuous search for new anti-HIV agents based on several chemical scaffolds, including nitrogenated heterocyclic pyrrole rings, which have been included in several compounds with antiretroviral activity. Thus, this review aims to describe pyrrole-based compounds with anti-HIV activity as a new potential treatment against AIDS, covering the period between 2015 and 2020. Our research allowed us to conclude that pyrrole derivatives are still worth exploring, as they may provide highly active compounds targeting different steps of the HIV-1 replication cycle and act with an innovative mechanism.

A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site

Allosteric integrase inhibitors (ALLINIs) are a class of experimental anti-HIV agents that target the noncatalytic sites of the viral integrase (IN) and interfere with the IN-viral RNA interaction during viral maturation. Here, we report a highly potent and safe pyrrolopyridine-based ALLINI, STP0404, displaying picomolar IC50 in human PBMCs with a >24,000 therapeutic index against HIV-1. X-ray structural and biochemical analyses revealed that STP0404 binds to the host LEDGF/p75 protein binding pocket of the IN dimer, which induces aberrant IN oligomerization and blocks the IN-RNA interaction. Consequently, STP0404 inhibits proper localization of HIV-1 RNA genomes in viral particles during viral maturation. Y99H and A128T mutations at the LEDGF/p75 binding pocket render resistance to STP0404. Extensive in vivo pharmacological and toxicity investigations demonstrate that STP0404 harbors outstanding therapeutic and safety properties. Overall, STP0404 is a potent and first-in-class ALLINI that targets LEDGF/p75 binding site and has advanced to a human trial.

A SHORT REVIEW ON HERBAL PRODUCTS ACTING AS ANTI-HIV AGENTS

Over the previous decade, considerable advancement has been made in research on the regular items having hostility to HIV movement. An assortment of optional metabolites got from natural origin demonstrated mild to strong anti-HIV properties. Nature has consistently given a wellspring of medications to different sicknesses. Various therapeutic plants have been accounted for to have against HIV. The investigation of regular items in biomedical exploration is not an advanced idea. vast numbers of the best medicinal therapeutic drugs are extracted from natural products and concentrated in HIV/AIDS. The Biomedical review has a long history of disclosure depending on the screen of medicinal spices and conventional medicines. It is essential to remember the clinical study convention to conclude Therapies based on these herbal products combat the negative view of alternative medicine as therapeutic remedies. This review addressed different herbal products that are having anti-HIV properties.

Cellular Therapy as Promising Choice of Treatment for COVID-19

In the pandemic of COVID-19, while living normals have been changing, there have been a huge effort globally to find out effective and safe treatment agents and vaccines. As of now, the advances show the progress in vaccine development, however the treatment of the COVID-19 is yet not fully specified. The drugs, i.e. antibiotics, antivirals, antimalarians, even anti-HIV agents which have been known already were taken out of the shelves and brought into use in different combinations. On the other hand, the cellular treatment, more specifically the mesenchymal stem cell therapy has been encouraged, resulting in various evidence published all over the world. This chapter aims to compile the published information, in means of methods, disease manifestations, results and limitations, about the stem cell treatment of the COVID-19 and to provide a source of harmonized reference for scientific society.