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. 2022 May 4;21(1):e126562.
doi: 10.5812/ijpr-126562. eCollection 2022 Dec.

Design, Synthesis, Docking Study, and Biological Evaluation of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbohydrazide Derivatives as Anti-HIV-1 and Antibacterial Agents

Omid Abdollahi  1 , Arash Mahboubi  2 , Zahra Hajimahdi  1 , Afshin Zarghi  1
Affiliations

Design, Synthesis, Docking Study, and Biological Evaluation of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbohydrazide Derivatives as Anti-HIV-1 and Antibacterial Agents

Omid Abdollahi et al. Iran J Pharm Res. .

Abstract

Background: The emergence of drug resistance to the existing antibacterial and anti-HIV-1 therapeutics has posed an urgent medical need to develop new molecules. We describe in this regard, a series of novel N'-arylidene-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbohydrazide derivatives with anti-HIV-1 and antibacterial activities were designed and synthesized in this study.

Methods: The synthesized compounds were evaluated for the blocking of both the IN ST process and cell-based HIV-1 replication. The synthesized compounds were also examined for in vitro antibacterial activities using the minimum inhibitory concentration (MIC) assay.

Results: The results revealed the moderate antibacterial activity of the synthesized compounds. Moreover, no significant integrase inhibitory and anti-HIV-1 activities were observed for the synthesized compounds at concentrations < 100 µM.

Conclusions: According to the docking analyses, the orientation of the designed scaffold in the active site of integrase is similar to the other inhibitors of the HIV integrase and can be regarded as an acceptable template for further structural modification to improve potencies.

Keywords: Anti-HIV-1; Antibacterial; Integrase; Synthesis, Quinoline.

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Conflict of interest statement

Conflict of Interests: Funding or Research support: Elite Researcher Grant Committee (Award No. 4002351) from the National Institute for Medical Research Development (NIMAD), Tehran, Iran. Employment: No; Personal financial interests: No; Stocks or shares in companies: No; Consultation fees: No; Patents: No; Personal or professional relations with organizations and individuals (parents and children, wife and husband, family relationships, etc.): No; Unpaid membership in a government or non-governmental organization: Yes; Are you one of the editorial board members or a reviewer of this journal? Yes.

Figures

Figure 1.
Figure 1.. Chemical structure of FDA-approved INSTIs inhibitors (Raltegravir 1, Elvitegravir 2, Dolutegravir 3, and Bictegravir 4)
Figure 2.
Figure 2.. Structure of IN inhibitors and designed molecules
Figure 3.
Figure 3.. Reagents and conditions: (i) diethyl malonate, DMF, 85°C, 5 h; (ii) NH2NH2.OH, ethanol, reflux, 2 h; (iii) benzaldehyde derivatives, H2SO4, ethanol, reflux, 2 h.
Figure 4.
Figure 4.. Bioassay data for a series of compounds 12a–o, indicating IN IC50 value for strand transfer inhibitory, EC50 values for inhibition of HIV-1 activity, and CC50 values for toxicity
Figure 5.
Figure 5.. 2D and 3D alignment of best-docked pose of Compound 12g (violet) in PFV IN active site
Figure 6.
Figure 6.. Overlay of Compound 12g (violet) on raltegravir (green) in PFV IN active site
See this image and copyright information in PMC

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