RESUMEN
2-Alkyl chromanone scaffold has become prominent in pharmaceuticals and natural compounds. Consequently, devising robust strategies for synthesizing 2-alkyl chromanones remains crucial. Here, multicomponent reactions were employed to synthesize 2-alkyl chromanones containing an oxazole moiety using 3-formylchromones, amines, and N-propargylamides as reactants. This method utilizes readily available feedstocks with a catalytic amount of Zn(OTf)2 and exhibits an impressive substrate scope compared to existing methods. Importantly, the synthesized compounds demonstrated highly selective anticancer activity against the DU145 cell line.
Asunto(s)
Antineoplásicos , Cromonas , Ácidos de Lewis , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Humanos , Cromonas/química , Cromonas/farmacología , Cromonas/síntesis química , Línea Celular Tumoral , Ácidos de Lewis/química , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Catálisis , Relación Estructura-ActividadRESUMEN
Macrophorins H (4) and L (5), two rare HMG-conjugate macrophorins along with three known macrophorins (1-3), three DMOA-derived meroterpenoids (6-8) and two ergosterol derivates (9-10) were isolated from sterilized rice medium cultured Penicillium sp. NX-05-G-3. Their structures were elucidated by 1D and 2D NMR. The cytotoxicities of all compounds were evaluated, and compounds 1 and 2 showed extensive cytotoxicity against human cancer cell lines Hela, SCC15, MDA-MB-453 and A549, with IC50 values ranging from 17.6 to 32.8 µM.
Asunto(s)
Ensayos de Selección de Medicamentos Antitumorales , Penicillium , Penicillium/química , Humanos , Estructura Molecular , Células HeLa , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Terpenos/farmacología , Terpenos/químicaRESUMEN
An unexpected Ugi cascade reaction was developed for the facile construction of γ-lactam-fused pyridone derivatives with high tolerance of substrates. A C(sp3)-N bond and a C(sp2)-C(sp2) bond were formed together, accompanied by a chromone ring-opening in Ugi adducts, under the basic conditions without any metal catalyst for the whole process. Screening data of several difficult-to-inhibit cancer cell lines demonstrated that 7l displayed a high cytotoxicity against HCT116 cells (IC50 = 5.59 ± 0.78 µM). Taken together, our findings revealed new insights into the molecular mechanisms underlying compound 7l and provided potential usage of this scaffold for cancer therapeutics.
Asunto(s)
Compuestos Heterocíclicos , Lactamas , Lactamas/farmacología , Piridonas/farmacología , Piridonas/química , MetalesRESUMEN
Five new 12-membered resorcylic acid lactone derivatives, penicimenolides A-E (1-5), one new ring-opened resorcylic acid lactone derivative penicimenolide F (6), and six known biogenetically related derivatives (7-12) were isolated from the culture broth of a strain of Penicillium sp. (NO. SYP-F-7919), a fungus obtained from the rhizosphere soil of Panax notoginseng collected from the Yunnan province of China. Their structures were elucidated by extensive NMR analyses, a modified Mosher's method, chemical derivatization and single crystal X-ray diffraction analysis. Compounds 2-4 exhibited potent cytotoxicity against the U937 and MCF-7 tumour cell lines and showed moderate cytotoxic activity against the SH-SY5Y and SW480 tumour cell lines. The substitution of an acetyloxy or 2-hydroxypropionyloxy group at C-7 significantly increased the cytotoxic activity of the resorcylic acid lactone derivatives. Subsequently, the possible mechanism of compound 2 against MCF-7 cells was preliminarily investigated by in silico analysis and experimental validation, indicating compound 2 may act as a potential MEK/ERK inhibitor. Moreover, proteomics analysis was performed to explore compound 2-regulated concrete mechanism underlying MEK/ERK pathway, which is still need further study in the future. In addition, compounds 2-4 and 7 exhibited a significant inhibitory effect on NO production induced by LPS.
Asunto(s)
Lactonas/metabolismo , Panax notoginseng , Penicillium/metabolismo , Rizosfera , Suelo , Apoptosis , Cristalografía por Rayos X , Humanos , Lactonas/química , Células MCF-7 , Estructura Molecular , Óxido Nítrico/biosíntesis , ProteómicaRESUMEN
The nonvolatile holographic storage of a near-stoichiometric LiNbO(3):Cu:Ce crystal with green light was investigated. With an increase in composition, improved nonvolatile holographic performance was obtained. The sensitivity S? of the near-stoichiometric LN(49.57):Cu:Ce crystal is 1 order of magnitude larger than the congruent crystal. And according to our research, Ce ions should be the deep centers of the LiNbO(3):Cu:Ce crystal.