scholarly journals HIV-1 Protease and Reverse Transcriptase Inhibitory Activities of Curcuma aeruginosa Roxb. Rhizome Extracts and the Phytochemical Profile Analysis: In Vitro and In Silico Screening

2021 ◽  
Vol 14 (11) ◽  
pp. 1115
Author(s):  
Chanin Sillapachaiyaporn ◽  
Panthakarn Rangsinth ◽  
Sunita Nilkhet ◽  
Nuntanat Moungkote ◽  
Siriporn Chuchawankul
Keyword(s):  
Antioxidant Activity ◽  
Reverse Transcriptase ◽  
In Silico ◽  
Active Sites ◽  
Profile Analysis ◽  
Total Phenolic ◽  
Inhibitory Activities ◽  
Anti Hiv ◽  
Hiv 1

Human immunodeficiency virus type-1 (HIV-1) infection causes acquired immunodeficiency syndrome (AIDS). Currently, several anti-retroviral drugs are available, but adverse effects of these drugs have been reported. Herein, we focused on the anti-HIV-1 activity of Curcuma aeruginosa Roxb. (CA) extracted by hexane (CA-H), ethyl acetate (CA-EA), and methanol (CA-M). The in vitro HIV-1 protease (PR) and HIV-1 reverse transcriptase (RT) inhibitory activities of CA extracts were screened. CA-M potentially inhibited HIV-1 PR (82.44%) comparable to Pepstatin A (81.48%), followed by CA-EA (67.05%) and CA-H (47.6%), respectively. All extracts exhibited moderate inhibition of HIV-1 RT (64.97 to 76.93%). Besides, phytochemical constituents of CA extracts were identified by GC-MS and UPLC-HRMS. Fatty acids, amino acids, and terpenoids were the major compounds found in the extracts. Furthermore, drug-likeness parameters and the ability of CA-identified compounds on blocking of the HIV-1 PR and RT active sites were in silico investigated. Dihydroergocornine, 3β,6α,7α-trihydroxy-5β-cholan-24-oic acid, and 6β,11β,16α,17α,21-Pentahydroxypregna-1,4-diene-3,20-dione-16,17-acetonide showed strong binding affinities at the active residues of both HIV-1 PR and RT. Moreover, antioxidant activity of CA extracts was determined. CA-EA exhibited the highest antioxidant activity, which positively related to the amount of total phenolic content. This study provided beneficial data for anti-HIV-1 drug discovery from CA extracts.

SYNTHESIS AND ANTI-HIV EVALUATION OF SUBSTITUTED INDOLE-3-CARBALDEHYDE DERIVATIVES

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (02) ◽  
pp. 18-26
Author(s):  
Pankaj Wadhwa ◽  
Priti Jain ◽  
Hemant R Jadhav
Keyword(s):  
Reverse Transcriptase ◽  
In Silico ◽  
Docking Studies ◽  
Significant Inhibition ◽  
Hiv Integrase ◽  
Starting Point ◽  
Hiv Integrase Inhibitors ◽  
Anti Hiv ◽  
Hiv 1

In the present study, a series of indole-3-carbaldehydes having substituted N-sulfonyl phenyl or Nphenacyl group was synthesized and evaluated for anti-HIV activity, in particular, in vitro and in silico HIV-1 integrase inhibition. Three compounds (8b, 8c and 8g) exhibited significant inhibition of HIV-1 IN (IC50 ≤5.32 μM). Molecular docking studies were also performed to justify the IN inhibition and in vitro in silico correlation was drawn. Compound 8b exhibited significant anti-HIV activity against HIV-1 strain IIIB (IC50 3.16 μM). HIV integrase inhibitors are also reported to inhibit reverse transcriptase. When 8b was further examined against various single and double mutant reverse transcriptase (RT) strains, it showed promising activity against E138K with IC50 value of 2.43 μM with safety index of 3. Therefore, compound 8b can be a starting point for the development of dual inhibitors of HIV integrase as well as reverse transcriptase.

scholarly journals Desain dan Studi In Silico Senyawa Turunan Kuwanon-H sebagai Kandidat Obat Anti-HIV

2018 ◽  
Vol 4 (1) ◽  
pp. 57-66
Author(s):  
Ruswanto Ruswanto ◽  
Tifa Nofianti ◽  
Richa Mardianingrum ◽  
Tresna Lestari
Keyword(s):  
Decision Tree ◽  
Reverse Transcriptase ◽  
In Silico ◽  
Morus Alba ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five ◽  
Anti Hiv ◽  
Hiv 1

Kuwanon-H merupakan senyawa flavonoid dari kulit akar  murbei (Morus alba L) yang secara in vitro berpotensi sebagai anti-HIV dibanding senyawa flavonoid lainnya yang terkandung dalam kulit akar murbei seperti morusin dan morusin 4′-glucosida. Telah dilakukan penelitian desain senyawa, penambatan molekular menggunakan ArgusLab 4.0.1 dengan metode ArgusDock, penerapan aturan Lipinski’s Rule of Five menggunakan Marvin Sketch 5.2.5.1dan uji toksisitas menggunakan aplikasi Toxtree secara in silico terhadap turunan senyawa kuwanon-H. Desain enam puluh senyawa turunan kuwanon-H dilakukan dengan cara model pendekatan Topliss pada rantai samping alifatiknya. Hasil penambatan ke-60 turunan senyawa pada reseptor HIV-1 Reverse Transcriptase (1REV) menunjukkan bahwa senyawa terbaik yaitu 3-[(2Z)-3-(siklopropilmetil)but-2-en-1-il]-8-[6-({3-[(2Z)-3-(siklopropilmetil)but-2-en-1-il]-2,4-dihidroksifenil}karbonil)-5-(2,4-di-hidroksilfenil)-3-metilsiklohek-2-en-1-il]-2-(2,4-dihidroksilfenil),7-dihidroksi-4H-kromen-4-on dengan nilai energi bebas yang lebih rendah (-12.5798 kkal/mol) dibandingkan ligan asli (-11.0445 kkal/mol) dan kuwanon-H (-11.0189 kkal/mol). Senyawa terbaik ini tidak memenuhi aturan Lipinski’s Rule of Five. Hasil prediksi uji toksisitas senyawa terbaik menurut parameter Cramer Rules termasuk kategori III, yaitu diprediksi memiliki toksisitas tinggi, menurut parameter Benigni/Bossa Rulebase diprediksi senyawa yang diuji tidak bersifat karsinogenik, genotoksik, dan nongenotoksik, sedangkan menurut parameter Kroes TTC decision tree diprediksi senyawa uji berpotensi toksik.DOI:http://dx.doi.org/10.15408/jkv.v4i1.6867 

scholarly journals Glycosylated Flavonoids from Psidium guineense as Major Inhibitors of HIV-1 Replication in vitro

2017 ◽  
Vol 12 (7) ◽  
pp. 1934578X1701200
Author(s):  
Joseph T Ortega ◽  
Omar Estrada ◽  
Maria L Serrano ◽  
Whendy Contreras ◽  
Giovannina Orsini ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Reverse Transcriptase ◽  
In Silico ◽  
Biological Activities ◽  
In Silico Prediction ◽  
Flavonoid Quercetin ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Hiv 1

Flavonoids are present in practically all plants and many biological activities have been described for them. The flavonoid quercetin is a common molecule for which anti-HIV activity has been demonstrated. Avicularin and guajaverin are derivatives of quercetin with a glycoside substituent in their structure. In this work, a mixture of both derivatives was purified from an extract of Psidium guinense. The mixture exhibited activity against HIV-1 in vitro, with an IC50 of approximately 8.5 μg/mL, which compares favorably with the IC50 of 53 μg/mL of quercetin. The mixture also inhibited HIV-1 reverse transcriptase (RT), with an IC50 of 7.2 μM, compared to 0.6 μM for quercetin. These results are in agreement with the in silico prediction for the interaction of these flavonoids with RT and suggest that the glycosylic moiety could favor the transport of the compound into the cell. However, the glycosidic moiety might be cleaved intracellularly, being the resultant quercetin responsible for the antiviral activity.

An Approach towards the Synthesis of Potential Metal-Chelating TSAO-T Derivatives as Bidentate Inhibitors of Human Immunodeficiency virus Type 1 Reverse Transcriptase

1998 ◽  
Vol 9 (5) ◽  
pp. 412-421 ◽  
Author(s):  
C Chamorro ◽  
M-J Camarasa ◽  
M-J Pérez-Pérez ◽  
E de Clercq ◽  
J Balzarini ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Parent Compound ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

Novel derivatives of the potent human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitor TSAO-T have been designed, synthesized and tested for their in vitro antiretro-viral activity against HIV. These TSAO-T derivatives have been designed as potential bidentate inhibitors of HIV-1 RT, which combine in their structure the functionality of a non-nucleoside RT inhibitor (TSAO-T) and a bivalent ion-chelating moiety (a β-diketone moiety) linked through an appropriate spacer to the N-3 of thymine of TSAO-T . Some of the new compounds have an anti-HIV-1 activity comparable to that of the parent compound TSAO-T, but display a markedly increased antiviral selectivity. There was a clear relationship between antiviral activity and the length of the spacer group that links the TSAO molecule with the chelating moiety. A shorter spacer invariably resulted in increased antiviral potency. None of the TSAO-T derivatives were endowed with anti-HIV-2 activity.

scholarly journals Anti-HIV-1 integrase potency of methylgallate from Alchornea cordifolia using in vitro and in silico approaches

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xavier Siwe-Noundou ◽  
Thommas M. Musyoka ◽  
Vuyani Moses ◽  
Derek T. Ndinteh ◽  
Dumisani Mnkandhla ◽  
...  
Keyword(s):  
In Silico ◽  
Anti Hiv ◽  
Hiv 1

Sensitivity of V75I HIV-1 reverse transcriptase mutant selected in vitro by acyclovir to anti-HIV drugs

AIDS ◽  
2010 ◽  
Vol 24 (2) ◽  
pp. 319-323 ◽  
Author(s):  
Moira A McMahon ◽  
Janet D Siliciano ◽  
Rahul M Kohli ◽  
Robert F Siliciano
Keyword(s):  
Reverse Transcriptase ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals In Vitro Antiviral Activity of the Novel, Tyrosyl-Based Human Immunodeficiency Virus (HIV) Type 1 Protease Inhibitor Brecanavir (GW640385) in Combination with Other Antiretrovirals and against a Panel of Protease Inhibitor-Resistant HIV

2007 ◽  
Vol 51 (9) ◽  
pp. 3147-3154 ◽  
Author(s):  
Richard Hazen ◽  
Robert Harvey ◽  
Robert Ferris ◽  
Charles Craig ◽  
Phillip Yates ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Protease Inhibitor ◽  
Reverse Transcriptase ◽  
In Vitro Assays ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT Brecanavir, a novel tyrosyl-based arylsulfonamide, high-affinity, human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI), has been evaluated for anti-HIV activity in several in vitro assays. Preclinical assessment of brecanavir indicated that this compound potently inhibited HIV-1 in cell culture assays with 50% effective concentrations (EC50s) of 0.2 to 0.53 nM and was equally active against HIV strains utilizing either the CXCR4 or CCR5 coreceptor, as was found with other PIs. The presence of up to 40% human serum decreased the anti-HIV-1 activity of brecanavir by 5.2-fold, but under these conditions the compound retained single-digit nanomolar EC50s. When brecanavir was tested in combination with nucleoside reverse transcriptase inhibitors, the antiviral activity of brecanavir was synergistic with the effects of stavudine and additive to the effects of zidovudine, tenofovir, dideoxycytidine, didanosine, adefovir, abacavir, lamivudine, and emtricitabine. Brecanavir was synergistic with the nonnucleoside reverse transcriptase inhibitor nevirapine or delavirdine and was additive to the effects of efavirenz. In combination with other PIs, brecanavir was additive to the activities of indinavir, lopinavir, nelfinavir, ritonavir, amprenavir, saquinavir, and atazanavir. Clinical HIV isolates from PI-experienced patients were evaluated for sensitivity to brecanavir and other PIs in a recombinant virus assay. Brecanavir had a <5-fold increase in EC50s against 80% of patient isolates tested and had a greater mean in vitro potency than amprenavir, indinavir, lopinavir, atazanavir, tipranavir, and darunavir. Brecanavir is by a substantial margin the most potent and broadly active antiviral agent among the PIs tested in vitro.

Sign in / Sign up

Export Citation Format

Share Document