首页|Pharmacophore-probe reaction guided purification to precisely identify electrophilic withanolides from Tubocapsicum anomalum Makino and their anti-TNBC activity
Pharmacophore-probe reaction guided purification to precisely identify electrophilic withanolides from Tubocapsicum anomalum Makino and their anti-TNBC activity
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NSTL
Elsevier
? 2022Pharmacophore-probe reaction guided purification strategy can reduce the workload of natural product chemistry and raise the probability of obtaining undescribed and high-bioactive target compounds. In this study, a probe of N-acetyl cysteine (NAC) was used to confirm the pharmacophore of Tubocapsicum anomalum (Franch. et Sav.) Makino. Furthermore, a thiol probe named 4-bromothiophenol (BTP) guided the discovery of three undescribed (1–3) and nine known (4–12) electrophilic withanolides (EWs) featured potential anti-triple negative breast cancer (TNBC) pharmacophore. Notably, co-incubation with BTP made the single crystals of EW conjugates much more accessible, which facilitated the absolute configuration determination of EWs. Electrophilic natural products with the potential of thio-alkylation modification and covalent inhibition key proteins in tumor cell signal transduction pathways may display significant antitumor activity. The MTT results indicated that most EWs showed anti-TNBC activity and were expected to develop anti-TNBC candidate drugs with high selectivity and novel mechanism.
Electrophilic withanolidesPharmacophore-probe reaction guidedSolanaceaeTriple negative breast cancerTubocapsicum anomalum (Franch. et Sav.) Makino
School of Pharmaceutical Sciences Zhejiang Chinese Medical University
Department of Clinical Pharmacology Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province Affiliated Hangzhou First People's Hospital Zhejiang University School of Medicine
NSTL
Elsevier
