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

2021 ◽  
Vol 21 ◽  
Author(s):  
Qingtai Chen ◽  
Chongchong Wu ◽  
Jinjin Zhu ◽  
Enzhong Li ◽  
Zhi Xu
Keyword(s):  
Therapeutic Potential ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Bioactive Molecules ◽  
Indole Derivatives ◽  
Chemical Structures ◽  
Hiv Drugs ◽  
Immunodeficiency Syndrome ◽  
Anti Hiv Agents ◽  
Anti Hiv

: 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.

Anti-HIV Integrase Inhibitors as New Candidates for the Treatment of COVID-19: A Narrative Literature Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Sofia Salari ◽  
Hedyieh Karbasforooshan ◽  
Hesamoddin Hosseinjani
Keyword(s):  
Treatment Options ◽  
World Health ◽  
Health Concern ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Integrase Inhibitors ◽  
Curative Therapy ◽  
Narrative Literature Review ◽  
Hiv Drugs ◽  
Anti Hiv

Background: The initial reports of a contagious novel Severe Acute Respiratory Syndrome – Coronavirus-2 (SARS-CoV-2) were proclaimed by Wuhan, Hubei province, China. This pathogen quickly became a health concern due to the World Health Organization's (WHO) alarm of its pandemic essence. Hence, there is an urgent need for efficacious and curative therapy against COVID-19. Objective: Theoretically, repurposing anti-viral drugs, specifically HIV treatments, could help the urgent need for treating COVID-19 due to the structural similarities of their critical enzyme substrates. Integrase inhibitors are a category of anti-HIV drugs that inhibit integrase strand transfer. In this review, we investigate the binding affinity and stability of raltegravir, dolutegravir, bictegravir, and elvitegravir in interactions with crucial enzymes of coronavirus. Methods: A literature search was conducted using scientific databases such as Web of Science, Medline (PubMed), Scopus, Google Scholar, and Embase from commencement to September 2020. The most relevant articles regarding the potential effects of integrase inhibitors against COVID-19 were gathered. Ultimately, ten original articles related to the searched terms were selected for this narrative review. Results: Apparently, in addition to the recent drugs prescribed to cure SARS-CoV-2, integrase inhibitors are promising drugs for repurposing in COVID-19 treatment. Several studies on raltegravir, dolutegravir, bictegravir and elvitegravir were conducted using virtual screening to guess either they are effective or not. Encouraging results were mostly reported for raltegravir and dolutegravir. Nevertheless, bictegravir and elvitegravir need more investigations. Conclusion: Further experimental and clinical studies of antiviral drugs are necessary to introduce appropriate treatment options for COVID-19.

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

2021 ◽  
Vol 14 (9) ◽  
pp. 893
Author(s):  
Maria da Conceição Avelino Dias Bianco ◽  
Debora Inacio Leite Firmino Marinho ◽  
Lucas Villas Boas Hoelz ◽  
Monica Macedo Bastos ◽  
Nubia Boechat
Keyword(s):  
New Drugs ◽  
Viral Load Suppression ◽  
Pyrrole Derivatives ◽  
Highly Active ◽  
First Case ◽  
Combined Antiretroviral Therapy ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Anti Hiv Agents ◽  
Anti Hiv

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.

scholarly journals In VitroDrug Combination Studies of Letermovir (AIC246, MK-8228) with Approved Anti-Human Cytomegalovirus (HCMV) and Anti-HIV Compounds in Inhibition of HCMV and HIV Replication

2015 ◽  
Vol 59 (6) ◽  
pp. 3140-3148 ◽  
Author(s):  
Steffen Wildum ◽  
Holger Zimmermann ◽  
Peter Lischka
Keyword(s):  
Human Cytomegalovirus ◽  
Treatment Strategies ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Severe Toxicity ◽  
Transplant Recipients ◽  
Hiv Drugs ◽  
Anti Hiv

ABSTRACTDespite modern prevention and treatment strategies, human cytomegalovirus (HCMV) remains a common opportunistic pathogen associated with serious morbidity and mortality in immunocompromised individuals, such as transplant recipients and AIDS patients. All drugs currently licensed for the treatment of HCMV infection target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Letermovir (AIC246, MK-8228) is a new anti-HCMV agent in clinical development that acts via a novel mode of action and has demonstrated anti-HCMV activityin vitroandin vivo. For the future, drug combination therapies, including letermovir, might be indicated under special medical conditions, such as the emergence of multidrug-resistant virus strains in transplant recipients or in HCMV-HIV-coinfected patients. Accordingly, knowledge of the compatibility of letermovir with other HCMV or HIV antivirals is of medical importance. Here, we evaluated the inhibition of HCMV replication by letermovir in combination with all currently approved HCMV antivirals using cell culture checkerboard assays. In addition, the effects of letermovir on the antiviral activities of selected HIV drugs, and vice versa, were analyzed. Using two different mathematical techniques to analyze the experimental data, (i) additive effects were observed for the combination of letermovir with anti-HCMV drugs and (ii) no interaction was found between letermovir and anti-HIV drugs. Since none of the tested drug combinations significantly antagonized letermovir efficacy (or vice versa), our findings suggest that letermovir may offer the potential for combination therapy with the tested HCMV and HIV drugs.

Pyrazole Containing Anti-HIV Agents: An Update

2022 ◽  
Vol 18 ◽  
Author(s):  
Sanjay Kumar ◽  
Shiv Gupta ◽  
Varsha Rani ◽  
Priyanka Sharma
Keyword(s):  
Review Article ◽  
Pyrazole Derivatives ◽  
Therapeutic Activity ◽  
Pharmacological Activities ◽  
Drug Discovery And Development ◽  
The World ◽  
Hiv Drugs ◽  
Anti Hiv Agents ◽  
Comprehensive Compilation ◽  
Anti Hiv

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.

scholarly journals Structure-Activity-Relationship and Mechanistic Insights for Anti-HIV Natural Products

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2070
Author(s):  
Ramandeep Kaur ◽  
Pooja Sharma ◽  
Girish K. Gupta ◽  
Fidele Ntie-Kang ◽  
Dinesh Kumar
Keyword(s):  
Natural Products ◽  
Mechanisms Of Action ◽  
Structure Activity ◽  
Immunodeficiency Virus ◽  
Ic50 Values ◽  
Acquired Immunodeficiency ◽  
Hiv Drugs ◽  
Immunodeficiency Syndrome ◽  
Anti Hiv ◽  
Made In

Acquired Immunodeficiency Syndrome (AIDS), which chiefly originatesfroma retrovirus named Human Immunodeficiency Virus (HIV), has impacted about 70 million people worldwide. Even though several advances have been made in the field of antiretroviral combination therapy, HIV is still responsible for a considerable number of deaths in Africa. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. Presently, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate drugs derived from plants as well as their derivatives. Several plants, such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity. Here, weattempt to summarize the main results, which focus on the structures of most potent plant-based natural products having anti-HIV activity along with their mechanisms of action and IC50 values, structure-activity-relationships and important key findings.

A Review on Quinoline Derived Scaffolds as Anti-HIV Agents

2019 ◽  
Vol 19 (6) ◽  
pp. 510-526 ◽  
Author(s):  
Nisha Chokkar ◽  
Sourav Kalra ◽  
Monika Chauhan ◽  
Raj Kumar
Keyword(s):  
Human Immunodeficiency Virus ◽  
Highly Active Antiretroviral Therapy ◽  
Fast Rate ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Quinolone Derivative ◽  
Immunodeficiency Syndrome ◽  
Anti Hiv Agents ◽  
Anti Hiv

After restricting the proliferation of CD4+T cells, Human Immunodeficiency Virus (HIV), infection persists at a very fast rate causing Acquired Immunodeficiency Syndrome (AIDS). This demands the vigorous need of suitable anti-HIV agents, as existing medicines do not provide a complete cure and exhibit drawbacks like toxicities, drug resistance, side-effects, etc. Even the introduction of Highly Active Antiretroviral Therapy (HAART) failed to combat HIV/AIDS completely. The major breakthrough in anti-HIV discovery was marked with the discovery of raltegravir in 2007, the first integrase (IN) inhibitor. Thereafter, the discovery of elvitegravir, a quinolone derivative emerged as the potent HIV-IN inhibitor. Though many more classes of different drugs that act as anti-HIV have been identified, some of which are under clinical trials, but the recent serious focus is still laid on quinoline and its analogues. In this review, we have covered all the quinoline-based derivatives that inhibit various targets and are potential anti-HIV agents in various phases of the drug discovery.

Anti-HIV Activity of Medicinal Herbs: Usage and Potential Development

2001 ◽  
Vol 29 (01) ◽  
pp. 69-81 ◽  
Author(s):  
Ji An Wu ◽  
Anoja S. Attele ◽  
Liu Zhang ◽  
Chun-Su Yuan
Keyword(s):  
Hiv Infection ◽  
Herbal Medicines ◽  
Immune Functions ◽  
Scutellaria Baicalensis Georgi ◽  
Potential Development ◽  
Research Findings ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Anti Hiv Agents ◽  
Anti Hiv

The acquired immunodeficiency syndrome (AIDS) is a result of human immunodeficiency virus (HIV) infection which subsequently leads to significant suppression of immune functions. AIDS is a significant threat to the health of mankind, and the search for effective therapies to treat AIDS is of paramount importance. Several chemical anti-HIV agents have been developed. However, besides the high cost, there are adverse effects and limitations associated with using chemotherapy for the treatment of HIV infection Thus, herbal medicines have frequently been used as an alternative medical therapy by HIV positive individuals and AIDS patients. The aim of this review is to summarize research findings for herbal medicines, which are endowed with the ability to inhibit HIV. In this article, we will emphasize a Chinese herbal medicine. Scutellaria baicalensis Georgi and its identified components (i.e. baicalein and baicalin) which have been shown to inhibit infectivity and replication of HIV. Potential development of anti-AIDS compounds using molecular modeling methods will also be discussed.

scholarly journals Maraviroc (Celsentri) in HIV treatment

2008 ◽  
Vol 9 (4) ◽  
pp. 219-222
Author(s):  
Viola Sacchi
Keyword(s):  
Reverse Transcriptase ◽  
Treatment Options ◽  
Hiv Treatment ◽  
New Drugs ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Fusion Inhibitors ◽  
Highly Active ◽  
Hiv Drugs ◽  
Immunodeficiency Syndrome

Since 1996, the prognosis of people living with immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) has improved significantly, due to highly active antiretroviral therapies (HAART) based on a combination of 3-4 anti-HIV drugs; the use ofthese drugs can achieve a durable suppression of HIV viraemia, turning HIV infection into a chronic illness. The three first licensed classes of antiretroviral agents are nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Until recently, treatment options for individuals developing resistanceto these drugs have been limited, but new drugs in existing classes (second generation NNRTIs and novel PIs) and novel classes of drugs (integrase inhibitors, CCR5 antagonists and fusion inhibitors) have become clinically available.

scholarly journals Efficient repositioning of approved drugs as anti-HIV agents using Anti-HIV-Predictor

2016 ◽  
Author(s):  
Shao-Xing Dai ◽  
Huan Chen ◽  
Wen-Xing Li ◽  
Yi-Cheng Guo ◽  
Jia-Qian Liu ◽  
...  
Keyword(s):  
Web Server ◽  
Female Infertility ◽  
Hiv Therapy ◽  
Link Type ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Syncytia Formation ◽  
Anti Hiv Agents ◽  
Anti Hiv

AbstractDevelopment of new, effective and affordable drugs against HIV is urgently needed. In this study, we developed a world’s first web server called Anti-HIV-Predictor (http://bsb.kiz.ac.cn:70/hivpre) for predicting anti-HIV activity of given compounds. This server is rapid and accurate (accuracy >93% and AUC > 0.958). We applied the server to screen 1835 approved drugs for anti-HIV therapy. Totally 67 drugs were predicted to have anti-HIV activity, 25 of which are anti-HIV drugs. Then we experimentally evaluated 35 predicted new anti-HIV compounds by assays of syncytia formation, p24 quantification, cytotoxicity. Finally, we repurposed 7 approved drugs (cetrorelix, dalbavancin, daunorubicin, doxorubicin, epirubicin, idarubicin and valrubicin) as new anti-HIV agents. The original indication of these drugs is involved in a variety of diseases such as female infertility and cancer. Anti-HIV-Predictor and the 7 repurposed anti-HIV agents provided here demonstrate the efficacy of this strategy for discovery of new anti-HIV agents.

scholarly journals Discovery of drugs that possess activity against feline leukemia virus

2012 ◽  
Vol 93 (4) ◽  
pp. 900-905 ◽  
Author(s):  
Willie M. Greggs ◽  
Christine L. Clouser ◽  
Steven E. Patterson ◽  
Louis M. Mansky
Keyword(s):  
Leukemia Virus ◽  
Treatment Options ◽  
Feline Leukemia Virus ◽  
Drug Classes ◽  
The Us ◽  
Us Fda ◽  
Hiv Drugs ◽  
Toxic Concentrations ◽  
Anti Hiv ◽  
Hiv 1

Feline leukemia virus (FeLV) is a gammaretrovirus that is a significant cause of neoplastic-related disorders affecting cats worldwide. Treatment options for FeLV are limited, associated with serious side effects, and can be cost-prohibitive. The development of drugs used to treat a related retrovirus, human immunodeficiency virus type 1 (HIV-1), has been rapid, leading to the approval of five drug classes. Although structural differences affect the susceptibility of gammaretroviruses to anti-HIV drugs, the similarities in mechanism of replication suggest that some anti-HIV-1 drugs may also inhibit FeLV. This study demonstrates the anti-FeLV activity of four drugs approved by the US FDA (Food and Drug Administration) at non-toxic concentrations. Of these, tenofovir and raltegravir are anti-HIV-1 drugs, while decitabine and gemcitabine are approved to treat myelodysplastic syndromes and pancreatic cancer, respectively, but also have anti-HIV-1 activity in cell culture. Our results indicate that these drugs may be useful for FeLV treatment and should be investigated for mechanism of action and suitability for veterinary use.

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