scholarly journals Novel Thiazolidin-4-ones as Potential Non-nucleoside Inhibitors of HIV-1 Reverse Transcriptase

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3821 ◽  
Author(s):  
Petrou ◽  
Eleftheriou ◽  
Geronikaki ◽  
Akrivou ◽  
Vizirianakis
Keyword(s):  
Reverse Transcriptase ◽  
Inhibitory Activity ◽  
Inhibitory Action ◽  
Docking Studies ◽  
Prediction Program ◽  
Ic50 Values ◽  
Acquired Immunodeficiency ◽  
Hiv Drugs ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Background: HIV is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), an infectious disease with increasing incidence worldwide. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) play an important role in the treatment of AIDS. Although, many compounds are already being used as anti-HIV drugs, research for the development of new inhibitors continues as the virus develops resistant strains. Methods: The best features of available NNRTIs were taken into account for the design of novel inhibitors. PASS (Prediction of activity spectra for substances) prediction program and molecular docking studies for the selection of designed compounds were used for the synthesis. Compounds were synthesized using conventional and microwave irradiation methods and HIV RT inhibitory action was evaluated by colorimetric photometric immunoassay. Results: The evaluation of HIV-1 RT inhibitory activity revealed that seven compounds have significantly lower ΙC50 values than nevirapine (0.3 μΜ). It was observed that the activity of compounds depends not only on the nature of substituent and it position in benzothiazole ring but also on the nature and position of substituents in benzene ring. Conclusion: Twenty four of the tested compounds exhibited inhibitory action lower than 4 μΜ. Seven of them showed better activity than nevirapine, while three of the compounds exhibited IC50 values lower than 5 nM. Two compounds 9 and 10 exhibited very good inhibitory activity with IC50 1 nM.

New Efavirenz Derivatives and 1,2,3-Triazolyl-phosphonates as Inhibitors of Reverse Transcriptase of HIV-1

2018 ◽  
Vol 18 (17) ◽  
pp. 1494-1505 ◽  
Author(s):  
Carolina C.P. Costa ◽  
Nubia Boechat ◽  
Monica M. Bastos ◽  
Fernando de C. da Silva ◽  
Andressa Marttorelli ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Triazole Ring ◽  
Biological Evaluation ◽  
World Health ◽  
Hiv Reverse Transcriptase ◽  
Ic50 Values ◽  
Health Organization ◽  
Hiv Drugs ◽  
Immunodeficiency Syndrome ◽  
New Compounds

Background: According to the World Health Organization (WHO), the fight against Acquired Immunodeficiency Syndrome (AIDS) is still one of the most significant challenges facing humanity. Worldwide, it is estimated that 36.7 million people are infected by the Human Immunodeficiency Virus (HIV). Despite the variety of available drugs, the search for new enzymatic inhibitors of HIV is still important due to the presence of adverse effects and the development of resistant strains. Therefore, the present study aimed to design, synthesize, and biologically evaluate novel inhibitors of HIV Reverse Transcriptase (RT). Materials and Methods: These compounds were obtained in two series, and compounds in both series contain a 1,2,3-triazole ring in their structures. The compounds in the first series are Efavirenz (EFV) analogues with the N-1 position substituted by another important fragment as described in the medicinal chemistry literature on anti-HIV drugs. The second series has a phosphonate chain similar to that in the structure of Tenofovir Disoproxil Fumarate (TDF). Results and Conclusion: The results of the biological evaluation showed that all compounds presented high RT inhibition values and lower or comparable inhibitory concentrations (the concentration needed to reduce the enzymatic activity by 50%, IC50 values, 0.8-1.9 µM). Among the compounds in the first series, the three with the lowest IC50 values had values between 0.8-0.9 µM, and of those in the second series, the most potent had an IC50 value of 1.1 µM; compounds in both series were equipotent to TDF (1.2 µM). Thus, the new compounds could be considered lead compounds for the development of new antiretroviral compounds.

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.

Non Nucleoside Reverse Transcriptase Inhibitors, Molecular Docking Studies and Antitubercular Activity of Thiazolidin-4-one Derivatives

2019 ◽  
Vol 15 (5) ◽  
pp. 433-444
Author(s):  
Trupti S. Chitre ◽  
Shital M. Patil ◽  
Anagha G. Sujalegaonkar ◽  
Kalyani D. Asgaonkar ◽  
Vijay M. Khedkar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antitubercular Activity ◽  
Docking Studies ◽  
Significant Activity ◽  
Molecular Docking Studies ◽  
Global Challenge ◽  
Control Drug ◽  
Ic50 Values ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Background:: Management of Co-existence of Acquired immunodeficiency syndrome and Tuberculosis has become a global challenge due to the emergence of resistant strains and pill burden. Objective: : Hence the aim of the present work was to design and evaluate compounds for their dual activity on HIV-1 and Tuberculosis (TB). Methods: : A series of seven, novel Thiazolidin-4-one derivatives were synthesized and evaluated for their anti-HIV and anti-tubercular activity along with Molecular docking studies. All the seven compounds displayed promising activity against the replication of HIV-1 in cell-based assays. The four most active compounds were further evaluated against X4 tropic HIV-1UG070 and R5 tropic HIV-1VB59 primary isolates. The binding affinity of all the designed compounds for HIV-RT and Mycobacterium tuberculosis Enol Reductase (MTB InhA) was gauged by molecular docking studies which revealed crucial thermodynamic interactions governing their binding. Results:: The CC50 values for the test compounds were in the range of, 15.08-34.9 μg/ml, while the IC50 values were in the range of 16.1-27.13(UG070; X4) and 12.03-23.64 (VB59; R5) μg/ml. The control drug Nevirapine (NVP) exhibited CC50 value of 77.13 μg/ml and IC50 value of 0.03 μg/ml. Amongst all these compounds, compound number 3 showed significant activity with a TI value of 2.167 and 2.678 against the HIV-1 X4 and the R5 tropic virus respectively. In anti-mycobacterial screening, the compounds proved effective in inhibiting the growth of both log phase and starved MTB cultures. Conclusion: : Compound 3 has been found to be active against HIV-1 as well as MTB.

4-Thiazolidinone derivatives as potent antimicrobial agents: microwave-assisted synthesis, biological evaluation and docking studies

MedChemComm ◽  
2015 ◽  
Vol 6 (2) ◽  
pp. 319-326 ◽  
Author(s):  
Eleni Pitta ◽  
Evangelia Tsolaki ◽  
Athina Geronikaki ◽  
Jovana Petrović ◽  
Jasmina Glamočlija ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Inhibitory Activity ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Microwave Assisted Synthesis ◽  
Microwave Assisted ◽  
Hiv 1

A series of ten thiazolidin-4-one derivatives was synthesized and evaluated for their antibacterial, antifungal and HIV-1 reverse transcriptase (RT) inhibitory activity.

scholarly journals Mechanism of polyoxometalate-mediated inactivation of DNA polymerases: an analysis with HIV-1 reverse transcriptase indicates specificity for the DNA-binding cleft

1996 ◽  
Vol 319 (2) ◽  
pp. 619-626 ◽  
Author(s):  
Stefanos G. SARAFIANOS ◽  
Ulrich KORTZ ◽  
Michael T. POPE ◽  
Mukund J. MODAK
Keyword(s):  
Dna Binding ◽  
Reverse Transcriptase ◽  
Dna Polymerases ◽  
Polymerase Activity ◽  
Docking Studies ◽  
Binary Complex ◽  
Binding Function ◽  
Ic50 Values ◽  
Binding Cleft ◽  
Hiv 1

The anti-DNA polymerase activity of a structural family of polyoxometalates has been determined. Two representative compounds of this family, possessing a saddle-like structure [(O3POPO3)4W12 O36]16- (polyoxometalate I) and [(O3PCH2PO3)4 W12O36]16- (polyoxometalate II) were found to inhibit all the DNA polymerases tested, with IC50 values ranging from 2 to 10 µM. A comparative study with HIV-1 reverse transcriptase (RT) and Klenow polymerase as representative DNA polymerases indicated that protection from inactivation was achieved by inclusion of DNA but not by deoxynucleotide triphosphates (dNTPs). Kinetic analysis revealed that the mode of HIV-1 RT inhibition is competitive with respect to DNA, and non-competitive with respect to dNTP binding. Cross-linking experiments confirmed that the inhibitors interfere with the DNA-binding function of HIV-1 reverse transcriptase. Interestingly, a number of drug-resistant mutants of HIV-1 RT exhibit a sensitivity to polyoxometalate comparable to the wild-type HIV-1 RT, suggesting that these polyoxometalates interact at a novel site. Because different polymerases contain DNA-binding clefts of various dimensions, it should be possible to modify polyoxometalates or to add a link to an enzyme-specific drug so that more effective inhibitors could be developed. Using a computer model of HIV-1 RT we performed docking studies in a binary complex (enzyme–polyoxometalate I) to propose tentatively a possible interacting site in HIV-1 RT consistent with the available biochemical results as well as with the geometric and charge constraints of the two molecules.

scholarly journals Comparative Studies of Various NNRTIs in the Active Site of Different HIV-1RT Receptors

2020 ◽  
Vol 3 (1) ◽  
pp. 33
Author(s):  
Priyanka Chandra ◽  
Swastika Ganguly ◽  
Soikata Karmakar
Keyword(s):  
Reverse Transcriptase ◽  
Active Site ◽  
Internal Standard ◽  
Binding Pocket ◽  
Docking Studies ◽  
Binding Modes ◽  
Wild Type ◽  
Acquired Immunodeficiency ◽  
Resistant Strains ◽  
Immunodeficiency Syndrome

HIV is one of the most deadly viruses known to humans and causes a disease, known as Acquired Immunodeficiency Syndrome (or, AIDS). There are only a handful of drugs which are totally effective against the virus. This is due to the enzyme reverse transcriptase present within the virus. Due to various mutations in the enzyme, the virus becomes unresponsive towards the drugs. In the present study, docking studies of the standard non-nucleoside reverse transcriptase inhibitors were performed in the non-nucleoside inhibitory binding pocket of reverse transcriptase enzymes of wild type and the resistant strains of HIV-1RT virus with PDB IDs 1RT2, 1KLM, 3BGR, and 1JLB, respectively, by using Autodock version 4.5.6. A comparison of different compounds docked into the active site of various HIV-1RT strains was carried out. The obtained results indicate that most of the compounds docked into the active site of the different receptors, such as 1RT2, 1KLM, 3BGR, and 1JLB, with good docking scores, are comparable to that of the internal standard (TNK 651) of the wild type strain of HIV-1 virus. A comparison was made based on the binding modes of the compounds in the active site of all the four receptors.

A Novel Ribonuclease with HIV-1 Reverse Transcriptase Inhibitory Activity from the Edible Mushroom Hygrophorus russula

2013 ◽  
Vol 170 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Mengjuan Zhu ◽  
Lijing Xu ◽  
Xiao Chen ◽  
Zengqiang Ma ◽  
Hexiang Wang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Inhibitory Activity ◽  
Edible Mushroom ◽  
Hiv 1

Design, Synthesis and Docking Studies of Thioimidazolyl Diketoacid Derivatives Targeting HIV-1 Integrase

2021 ◽  
Vol 17 ◽  
Author(s):  
Nafiseh Karimi ◽  
Rouhollah Vahabpour Roudsari ◽  
Zahra Hajimahdi ◽  
Afshin Zarghi
Keyword(s):  
Drug Target ◽  
Enzyme Assay ◽  
Binding Mode ◽  
Docking Studies ◽  
Integrase Inhibitors ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Novel Structures ◽  
Anti Hiv ◽  
Hiv 1

Background: Integrase enzyme is a validated drug target to discover novel structures as anti-HIV-1 agents. Objective: Novel series of thioimidazolyl diketo acid derivatives characterizing various substituents at N-1 and 2-thio positions of central ring were developed as HIV-1 integrase inhibitors. Results: The obtained molecules were evaluated in the enzyme assay, displaying promising integrase inhibitory activity with IC50 values ranging from 0.9 to 7.7 M. The synthesized compounds were also tested for antiviral activity and cytotoxicity using HeLa cells infected by the single-cycle replicable HIV-1 NL4-3. Conclusion: The most potent compound was 18i with EC50=19 µM, IC50 0.9 µM and SI= 10.5. Docking studies indicated that the binding mode of the active molecule is well aligned with the known HIV-1 integrase inhibitors.

scholarly journals Settings for identifying recent HIV infections: the Portuguese experience

2008 ◽  
Vol 13 (36) ◽  
Author(s):  
H Cortes Martins ◽  
M T Paixão
Keyword(s):  
Hiv Infections ◽  
Cross Sectional Study ◽  
Western European Country ◽  
Reference Laboratory ◽  
Cross Sectional ◽  
Sexually Transmitted ◽  
Aids Epidemic ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Portugal has been the western European country with the highest rate of notified acquired immunodeficiency syndrome (AIDS) cases since 1999 and human immunodeficiency virus (HIV) infection cases since 2000. Nonetheless, exact information on the magnitude and trends of recently acquired infections is missing. In a cross-sectional study we aimed to determine HIV prevalence, the proportion of recently acquired infections and the incidence among patients attending a Sexually Transmitted Infections (STI) clinic and among HIV positive cases tested at the AIDS Reference Laboratory (ARL), by using the Avidity Index (AI) of antibodies to identify recent HIV-1 seroconversions. Demographic and behavioural data were collected. At the STI clinic 253 patients were enrolled, 16 were found to be HIV infected (14 HIV-1, 2 HIV-2) and a prevalence of 6.3% was obtained. Four recent HIV-1 infections were identified and the HIV-1 incidence was 3.3% per year. At the ARL, 332 newly diagnosed cases of HIV-1 infection were studied, 59 (17.8%) were recent infections and an annual incidence of 4.1% was estimated. These findings support STI clinics as key sentinel sites for recently acquired HIV infections and illustrate the viability of testing for recent HIV infections in these settings and reinforce the value of this method in the surveillance for better monitoring current trends of the HIV/AIDS epidemic in Portugal.

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