BackgroundRhodanines and quinazolinones have been reported to possess various pharmacological activities.ResultsA novel series of twenty quinazolinone-based rhodanines were synthesized via Knoevenagel condensation between 4-[3-(substitutedphenyl)-3,4-dihydro-4-oxoquinazolin-2-yl)methoxy]substituted-benzaldehydes and rhodanine. Elemental and spectral analysis were used to confirm structures of the newly synthesized compounds. The newly synthesized compounds were biologically evaluated for in vitro cytotoxic activity against the human fibrosarcoma cell line HT-1080 as a preliminary screen using the MTT assay.ConclusionsAll the target compounds were active, displaying IC50 values roughly in the range of 10–60 µM. Structure–activity relationship study revealed that bulky, hydrophobic, and electron withdrawing substituents at the para-position of the quinazolinone 3-phenyl ring as well as methoxy substitution on the central benzene ring, enhance cytotoxic activity. The four most cytotoxic compounds namely, 45, 43, 47, and 37 were further tested against two human leukemia cell lines namely, HL-60 and K-562 and showed cytotoxic activity in the low micromolar range with compound 45 being the most active, having IC50 values of 1.2 and 1.5 μM, respectively. Interestingly, all four compounds were devoid of cytotoxicity against normal human fibroblasts strain AG01523, indicating that the synthesized rhodanines may be selectively toxic against cancer cells. Mechanistic studies revealed that the most cytotoxic target compounds exhibit pro-apoptotic activity and trigger oxidative stress in cancer cells.
The NLRP3 inflammasome is currently an exciting target for drug discovery due to its role in various inflammatory diseases; however, to date, no NLRP3 inhibitors have reached the clinic. Several studies have used natural products as hit compounds to facilitate the design of novel selective NLRP3 inhibitors. Here, we review selected natural products reported in the literature as NLRP3 inhibitors, with a particular focus on those targeting gout. To complement this survey, we also report a virtual screen of the ZINC20 natural product database, predicting favored chemical features that can aid in the design of novel small molecule NLRP3 inhibitors.
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