Garcinol from Garcinia indica inhibits HIV‐1 reverse transcriptase‐associated ribonuclease H

Abstract

The bioactive components of Garcinia indica, garcinol (camboginol), and isogarcinol (cambogin), are suitable drug candidates for the treatment of various human diseases. HIV‐1‐RNase H assay was used to study the RNase H inhibition by garcinol and isogarcinol. Docking of garcinol into the active site of the enzyme was carried out to rationalize the difference in activities between the two compounds. Garcinol showed higher HIV‐1‐RNase H inhibition than the known inhibitor RDS1759 and retained full potency against the RNase H of a drug‐resistant HIV‐1 reverse transcriptase form. Isogarcinol was distinctly less active than garcinol, indicating the importance of the enolizable β‐diketone moiety of garcinol for anti‐RNase H activity. Docking calculations confirmed these findings and suggested this moiety to be involved in the chelation of metal ions of the active site. On the basis of its HIV‐1 reverse transcriptase‐associated RNase H inhibitory activity, garcinol is worth being further explored concerning its potential as a cost‐effective treatment for HIV patients.

Garcinia kola: a critical review on chemistry and pharmacology of an important West African medicinal plant

“…valproate Garcinol reduced seizure scores and mortality rates, downregulated apoptotic proteins and caspase-3, enhanced GABA A and GAD65 while it suppressed BDNF and TrkB, and enhanced the performance of mice in Morris water maze tests Hao et al ( 2016 ) Neuropathic pain Lumbar fifth spinal nerve ligation (SNL) induced Sprague–Dawley rats 100 μg/kg intrathecally N/A Garcinol inhibited the SNL-induced microglia activation in the spinal cord and ameliorated the neuropathic pain, attenuated the neuroinflammation (expression of interleukin interleukins, iNOS)/NO, and COX-2/PGE 2 ), and inhibited lipopolysaccharide-stimulated inflammatory response in microglia in vitro Wang et al ( 2017 ) In vitro Primary rat microglial cells 3.04 mg/mL N/A Drug withdrawal Reconsolidation of a cocaine-associated memory Sprague–Dawley rats 10 mg/kg i.p N/A Garcinol impaired the reconsolidation of the cocaine-associated cue memory. It had no effect on drug-induced cocaine-seeking, but was capable of blocking the initial conditioned reinforcing properties of the cue and prevented acquisition of new response Monsey et al ( 2017 ) In vitro antiviral activity HIV—p300; PCAF transcriptional coactivators IC 50 = 4.5 µg/mL N/A Garcinol inhibited histone acetylation of HIV infected cells, and consequently inhibited the multiplication of HIV Mantelingu et al ( 2007 ) HIV‐1 reverse transcriptase IC 50 = 5.2 µg/mL RDS1759 IC 50 = 3.1 µg/mL (8.7 μM) Garcinol showed inhibition of HIV-1 reverse transcriptase-associated ribonuclease H enzyme Corona et al ( 2021 ) Inf...…”

Synthesis and Antiviral Efficacy of Pyrimidine Analogs Targeting Viral Pathways

“…Apart from this, in literature, many natural products and synthetic compounds have been reported for their strong inhibition towards these viruses [96–99] . Despite advanced research, there is a need for small molecules, bioactive natural products, and transitional medicine to reduce viral transmission like SARS‐CoV‐2.…”

“…Apart from this, in literature, many natural products and synthetic compounds have been reported for their strong inhibition towards these viruses. [96][97][98][99] Despite advanced research, there is a need for small molecules, bioactive natural products, and transitional medicine to reduce viral transmission like SARS-CoV-2. As a component of the COVID-19 treatment regimen, pyrimidine analogs targeting viral pathways may demonstrate potential value in countering SARS-CoV-2 infection.…”

Versatile anti-infective properties of pyrido- and dihydropyrido[2,3-d]pyrimidine-based compounds

“…Analogously to the synthesis of 3i, compound 3m was obtained from 2m (36 (33) [M + ], 435 (100) [M + ], 420 (22), 342 (27).…”