Inhibitory Activity of Flavonoid Scaffolds on SARS-CoV-2 3CLpro: Insights from the Computational and Experimental Investigations.

The emergence of the COVID-19 situation has become a global issue due to the lack of effective antiviral drugs for treatment. Flavonoids are a class of plant secondary metabolites that have antiviral activity against SARS-CoV-2 through inhibition of the main protease (3CLpro). In this study, 22 flavonoids obtained from natural sources and semisynthetic approaches were investigated for their inhibitory activity against SARS-CoV-2 3CLpro, along with cytotoxicity on Vero cells. The protein-ligand interactions were examined using molecular dynamics simulation. Moreover, QSAR analysis was conducted to clarify the structural effects on bioactivity. Accordingly, the in vitro investigation demonstrated that four flavonoids, namely, tectochrysin (7), 6″,6″-dimethylchromeno-[2″,3″:7,8]-flavone (9), panduratin A (19), and genistein (20), showed higher protease inhibitory activity compared to the standard flavonoid baicalein. Finally, our finding suggests that genistein (20), an isoflavone discovered in Millettia brandisiana, has potential for further development as a SARS-CoV-2 3CLpro inhibitor.

Multifunctional effect of flavonoids from Millettia brandisiana against Alzheimer's disease pathogenesis.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and neuronal death. Fifteen flavonoids from Millettia brandisiana were evaluated for the multifunctional effect against AD pathogenesis, including butyrylcholine esterase (BuChE) inhibition, anti-amyloid beta (Aß) aggregation and neuroprotection against hydrogen peroxide (H2O2) toxicity in differentiated human neuroblastoma SH-SY5Y cell. To understand the mechanism and structure-activity relationship, binding interactions between flavonoids and the BuChE and Aß were investigated in silico. Furthermore, drug-likeness properties and ADMET parameters were evaluated in silico using SwissADME and pKCSM tools. All flavonoids exhibit a good drug-likeness profile. Six flavonoids have potency in BuChE inhibition, and four flavonoids show potency in anti-Aß aggregation. Flavonoids with the 6″,6″-dimethylchromeno- [2″,3″:7,8]-flavone structure show a favorable multifunctional effect. In silico analysis showed that flavonoids can bind in various positions to the catalytic triad, anionic site, and acyl pocket. In Aß1-42, potential flavonoids can attach to the central hydrophobic region and the C terminal hydrophobic and interfere with Aß interchain hydrogen binding. When compared together, it can inhibit multifunctional action with a favorable ADMET parameter and drug-likeness profile. In addition, candidine can prevent neuronal damage in differentiated SH-SY5Y neuroblastoma cells induced by H2O2 in a dose-dependent manner.

Correction: Structural modification of olibergin A, an isoflavonoid, from Dalbergia stipulacea Roxb. and its cytotoxicity.

[This corrects the article DOI: 10.1039/D2RA02865D.].

Structural modification of olibergin A, an isoflavonoid, from Dalbergia stipulacea Roxb. and its cytotoxicity.

Fifteen derivatives were synthesized from olibergin A, a major isoflavonoid isolated from the stems of Dalbergia stipulacea Roxb. All compounds were evaluated for cytotoxicity against HCT-116, HT-29, MCF-7 and vero cell lines using MTT assay. Cytotoxicity results showed 5-hydroxy-7,2',4',5'-tetramethoxyisoflavone (5) was the most active with IC50 values of 19.03 ± 0.70, 10.83 ± 1.65, 12.53 ± 0.70 and 13.53 ± 0.84 µM against HCT-116, HT-29, MCF-7 and vero cell lines, respectively. It should be noted that 5-hydroxy-7,2',4',5'-tetramethoxyisoflavone (5) showed two times less toxicity against vero cells than the cisplatin standard (IC50 = 6.55 ± 0.81 µM) while 5 and cisplatin exhibited nearly equal cytotoxicity against the MCF-7 cell line. 5,7,2',4',5'-Pentamethoxyisoflavanone (10) showed an IC50 value of 30.34 ± 1.15 µM against the HCT-116 cell line and exhibited weak cytotoxicity against normal cells, the vero cell line. In addition, 5,7,4'-trihydroxy-2',5'-dimethoxyisoflavan oxime (13) demonstrated cytotoxicity against HT-29 cells with an IC50 value of 31.41 ± 1.38 µM and displayed weak activity toward the vero cell line. The information revealed that these compounds were suitable for development to anticancer agents against HCT-116, HT-29 and MCF-7 cell lines.

Brandisianones F and G from Millettia brandisiana Kurz and their cytotoxicity.

A new flavanone and a new chalcone, brandisianones F and G, were purified from the roots of Millettia brandisiana Kurz, moreover, sixteen known compounds were found. The chemical structures of all isolated compounds were identified using spectroscopic methods including 1D-NMR, 2D-NMR, MS, IR and CD data. Chalcone 15 exhibited the most cytotoxic activity against liver cancer, HepG2, and cholangiocarcinoma, KKU-M156, cell lines with IC50 values of 1.74 ± 0.91 and 1.95 ± 0.95 µg/mL, respectively. Chalcones 2, 14, 16 and 18 as well as flavones 5, 6 and 12 showed moderate cytotoxicity with IC50 values ranging from 5.39 to 14.00 µg/mL.[Formula: see text].

A new xanthone from the fungus Apiospora montagnei.

A new xanthone derivative, methyl 8-hydroxy-3-hydroxymethylxanthone-1-carboxylate (1), and seven known compounds, 8-hydroxy-3-methylxanthone-1-carboxylate (2), methyl 8-hydroxy-6-methylxanthone-1-carboxylate (3), ergosterol (4), cyathisterone (5), ergosta-4,6,8(14),22-tetraen-3-one (6), calvasterone (7) and 2-hexyl-3-methylmaleic anhydride (8) were first isolated from the fungus Apiospora montagnei. Their structures were elucidated on the basis of spectroscopic analysis (UV, IR, MS, 1D, and 2D NMR). Compounds 5 and 6 showed weak to very weak cytotoxicity against cancer cell lines, NCI-H187 and KB.