Synthesis and Antiretroviral Activity of 6-Acetyl-coumarin Derivatives against HIV-1 Infection

Abstract

Srivastav, et al.: Synthesis and Antiretroviral Activity of 6-Acetyl-coumarin Derivatives A series of 6-acetyl-coumarin derivatives (2a-n) were synthesized and evaluated for antiretroviral activity in C8166 T-cell line infected with HxBru-Gluc strain of human immunodeficiency virus-1. Michael Addition followed by re-aromatization and subsequent acid-induced elimination of water leads to the formation of coumarin intermediate, which undergoes Claisen-Schmidt condensation with substituted bezaldehydes using silica sulphuric acid as a catalyst to form 6-acetyl-coumarin derivatives, 2a-n. In silico absorption, distribution, metabolism, excretion and toxicity parameters of compounds 2a-n were found within their reference limits. All synthesized compounds were devoid of cytotoxicity as they have shown cell viability count more than 80 % in cytotoxicity assay. Compounds 2a, 2g and 2h showed potent inhibitory activity against human immunodeficiency virus infection with IC 50 value of 4.7, 4.5 and 0.35 µM, respectively. It was found that electron-withdrawing group at phenyl ring, attached to the coumarin nucleus was crucial for activity against human immunodeficiency virus. The present study may be helpful in the development of some potent antiretroviral agents.

Coumarin: An emerging antiviral agent

“…Anti-viral action and mechanism of 6-acetyl-coumarin analogues have been studied on human C8166 cells. It has been found that electronegative substituent at the phenyl ring connected with coumarin central motif plays a very important role in the anti-HIV activity of coumarin [46]. Further, QSAR and Docking approaches indicated that Coumarin negatively regulates 3' processing and integrase enzyme of HIV.…”

“…Further, expression of the HIV-1 receptor (CD4) and co-receptors (CXCR4 and CCR5) was downregulated which may also contribute to blocking the HIV entry [53,55]. 4-phenylcoumarin derivatives called neoflavanoids were synthesized and their anti-HIV effects were assessed on MT-2 infected cells in vitro [46]. It suggested that the acyl group was essential for the inhibition of both the Tat and NF-kB pathway [56].…”

Synthesis, complete assignment of 1H- and 13C-NMR spectra and antioxidant activity of new azine derivative bearing coumarin moiety

“…To determine these activities, an enormous number of synthesized coumarin derivatives are subjected to various assaying. They showed a remarkably wide spectrum of antimicrobial (Al-Haiza et al, 2003;Medimagh-Saidana et al, 2015;López-Rojas et al, 2018), antifungal (Guerra et al, 2015;Forezi et al, 2018), anti-HIV (Kirkiacharian et al, 2002;Su et al, 2006;Srivastav et al, 2018), anticoagulant (Manolov & Danchev, 1999), antitumor (Nofal et al, 2000;Fayed et al, 2019) and anti-inflammatory (Kontogiorgis & Hadjipavlou-Litina, 2005). Also, many coumarin derivatives are used as optical brightening agents and food supplements (Wang et al, 2013;Zhang et al, 2016).…”

Microwave assisted synthesis, characterization and investigation of antibacterial activity of 3-(5-(substituted-phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-chromen-2-one derivatives

“…Due to their broad ranges of biological activities, they have also enjoyed laboratory preparation both in micro-scale and large-scale media. Coumarin and its fused derivatives have been reported to possess diverse pharmacological activities such as antimicrobial (Widelski et al, 2018), anticancer (Bouhenna et al, 2018), anti-inflammatory (Chavan & Hosamani, 2018), anti-HIV (Srivastav et al, 2018), antioxidant (P erez-Cruz et al, 2018), antimalarial (Hu et al, 2018), antitumor (Amin et al, 2018), anti-HCV (Peng et al, 2013), antihyperlipidemic (Iyer & Patil, 2014) and antitubercular (Patel et al, 2013) activities.…”