Design, Synthesis, Docking Studies and Biological Activities Novel 2,3- Diaryl-4-Quinazolinone Derivatives as Anti-HIV-1 Agents

Background: Although major efforts have been devoted to the effective treatment of HIV-1 infection, it has remained one of the leading causes of deaths around the world. So, development of anti-HIV-1 agents featuring novel structure is essential. Objective: To synthesize novel quinazolinone derivatives and evaluate their anti-HIV-1 activity. Method: In this study, we designed and synthesized a series of novel 2,3-diaryl-4-quinazolinone derivatives using a one-pot multicomponent reaction. Then, the resulting derivatives were evaluated for anti-HIV-1 activity using Hela cell-based single-cycle replication assay. Results: Most of the compounds showed efficacy against HIV-1 replication and the compound 9c exhibited the highest activity with EC50 value of 37 μM. Docking studies indicated that synthesized compounds can interact with the key residues of the HIV-1 integrase active site. Binding of the most active compound was consistent with the HIV-1 integrase inhibitors. Conclusion: Based on our results, these derivatives represent novel lead compounds for the development of new promising anti-HIV-1 agents.

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Design, Synthesis and Docking Studies of Novel 1, 2, 3-Triazolyl Phenylthiazole Analogs as Potent Anti-HIV-1 NNRT Inhibitors

Medicinal Chemistry ◽

10.4172/2161-0444.1000467 ◽

2017 ◽

Vol 7 (10) ◽

Author(s):

Suresh C Jadhavar ◽

Sujit G Bhansali ◽

Shivaji B Patwari ◽

Sudhakar R Bhusare ◽

Hanmant M Kasralikar

Keyword(s):

Docking Studies ◽

Design Synthesis ◽

Anti Hiv ◽

Hiv 1

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

Medicinal Chemistry ◽

10.2174/1573406417666210929124944 ◽

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.

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Design, Synthesis and Docking Studies of New 4-hydroxyquinoline-3-carbohydrazide Derivatives as Anti-HIV-1 Agents

Drug Research ◽

10.1055/s-0033-1334964 ◽

2013 ◽

Vol 63 (04) ◽

pp. 192-197 ◽

Cited By ~ 6

Author(s):

Z. Hajimahdi ◽

R. Zabihollahi ◽

M. Aghasadeghi ◽

A. Zarghi

Keyword(s):

Docking Studies ◽

Design Synthesis ◽

Anti Hiv ◽

Hiv 1

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Novel quinolone-3-carboxylic acid derivatives as anti-HIV-1 agents: design, synthesis, and biological activities

Medicinal Chemistry Research ◽

10.1007/s00044-016-1631-x ◽

2016 ◽

Vol 25 (9) ◽

pp. 1861-1876 ◽

Cited By ~ 14

Author(s):

Z. Hajimahdi ◽

R. Zabihollahi ◽

M. R. Aghasadeghi ◽

S. Hosseini Ashtiani ◽

A. Zarghi

Keyword(s):

Carboxylic Acid ◽

Biological Activities ◽

Design Synthesis ◽

Anti Hiv ◽

Hiv 1

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Design, synthesis, and docking studies of new 2-benzoxazolinone derivatives as anti-HIV-1 agents

Medicinal Chemistry Research ◽

10.1007/s00044-017-1969-8 ◽

2017 ◽

Vol 26 (11) ◽

pp. 2718-2726 ◽

Cited By ~ 9

Author(s):

Mahdieh Safakish ◽

Zahra Hajimahdi ◽

Rezvan Zabihollahi ◽

Mohammad R. Aghasadeghi ◽

Rouhoullah Vahabpour ◽

...

Keyword(s):

Docking Studies ◽

Design Synthesis ◽

Anti Hiv ◽

Hiv 1

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Novel 4-Oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic Acid Derivatives as HIV-1 Integrase Inhibitors: Synthesis, Docking studies, Molecular Dynamics Simulation and Biological Activities.

Medicinal Chemistry ◽

10.2174/1573406416666200909104616 ◽

2020 ◽

Vol 16 ◽

Author(s):

Elnaz Ebrahim Zadeh ◽

Rouhollah Vahabpour ◽

Amirreza Dowlati Beirami ◽

Zahra Hajimahdi ◽

Afshin Zarghi

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Carboxylic Acid ◽

Biological Activities ◽

Docking Studies ◽

Dynamics Simulation ◽

Lead Compounds ◽

Anti Hiv ◽

Hiv 1

Background: HIV-1 integrase (IN) has been considered as an important target for the development of novel antiHIV-1 drugs. Objective: The aim of study is to design a novel groups of HIV IN inhibitors Method: In this study, we presented a novel series of 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic acid derivatives by structural modification of N-arylindole -diketoacids as a well-known group of IN inhibitors. Results: Based on in-vitro anti-HIV-1 activity in cell-based assay, compounds 5, 6a and 6k displayed moderate to good inhibitory activity with EC50 values of 4.14, 1.68 and 0.8 M, respectively. However, integrase inhibition assay showed that most of analogues did not have significant effects against integrase enzyme except compound 5 with IC50 value of 45 M. Our results indicated that compound 6k was the best one among synthesized compounds with an EC50 of 0.8 M and SI of 175. Docking and molecular dynamics simulation studies were also performed to provide some insights into probable mechanism of tested compounds. Conclusion: These findings suggest that 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic acid derivatives may consider as promising lead compounds for development of new anti-HIV-1 drugs.

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Design, synthesis and anti-HIV-1 evaluation of hydrazide-based peptidomimetics as selective gelatinase inhibitors

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2016.03.043 ◽

2016 ◽

Vol 24 (9) ◽

pp. 2125-2136 ◽

Cited By ~ 23

Author(s):

Liang Yang ◽

Ping Wang ◽

Ji-Feng Wu ◽

Liu-Meng Yang ◽

Rui-Rui Wang ◽

...

Keyword(s):

Design Synthesis ◽

Anti Hiv ◽

Hiv 1

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Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel 4-[4-Arylpyridin-1(4H)-yl]benzoic Acid Derivatives as Anti-HIV-1 Agents

Chemistry & Biodiversity ◽

10.1002/cbdv.201700295 ◽

2017 ◽

Vol 14 (12) ◽

pp. e1700295 ◽

Cited By ~ 8

Author(s):

Saghi Sepehri ◽

Sepehr Soleymani ◽

Rezvan Zabihollahi ◽

Mohammad R. Aghasadeghi ◽

Mehdi Sadat ◽

...

Keyword(s):

Molecular Docking ◽

Benzoic Acid ◽

Docking Studies ◽

Biological Evaluation ◽

Molecular Docking Studies ◽

Benzoic Acid Derivatives ◽

Anti Hiv ◽

Hiv 1

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Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors

International Journal of Molecular Sciences ◽

10.3390/ijms21249623 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9623

Author(s):

Łukasz Szczukowski ◽

Edward Krzyżak ◽

Adrianna Zborowska ◽

Patrycja Zając ◽

Katarzyna Potyrak ◽

...

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

One Pot ◽

Design Synthesis ◽

Biological Studies ◽

Cox 2 ◽

Anti Inflammatory ◽

Dna Strand ◽

Cox 2 Inhibitors

The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-d]pyridazinone which strongly inhibit cyclooxygenase, have better affinity to COX-2 isoenzyme and exert promising anti-oxidant activity. These findings encouraged us to perform further optimization of that structure. Herein, we present the design, synthesis, molecular docking, spectroscopic, and biological studies of novel pyrrolo[3,4-d]pyridazinone derivatives bearing 4-aryl-1-(1-oxoethyl)piperazine pharmacophore 5a,b–6a,b. The new compounds were obtained via convenient, efficient, one-pot synthesis. According to in vitro evaluations, novel molecules exert no cytotoxicity and act as selective COX-2 inhibitors. These findings stay in good correlation with molecular modeling results, which additionally showed that investigated compounds take a position in the active site of COX-2 very similar to Meloxicam. Moreover, all derivatives reduce the increased level of reactive oxygen and nitrogen species and prevent DNA strand breaks caused by oxidative stress. Finally, performed spectroscopic and molecular docking studies demonstrated that new compound interactions with bovine serum albumin (BSA) are moderate, formation of complexes is in one-to-one ratio, and binding site II (subdomain IIIA) is favorable.

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