1. Controllable transformation of indoles using iodine(III) reagent
Yinxiang Jian, Peng Liang, Xiaoyan Li, Huawu Shao, Xiaofeng Ma Org Biomol Chem. 2022 Dec 21;21(1):179-186. doi: 10.1039/d2ob01951e.
Herein, an efficient and highly functional group-compatible procedure for controllable transformation of indoles by the combination of phenyliodine bis(trifluoroacetate) (PIFA) with n-Bu4NCl·H2O (TBAC) was exploited. Through controlling the amount of PIFA and TBAC from one to three equivalents, 3-chloro-indoles, 3-chloro-2-oxindoles, and 3,3-dichloro-2-oxindoles were obtained, respectively, in satisfactory to excellent yields. The advantages of the protocol include mild conditions, facile process with short reaction time, high yields, satisfactory functional group tolerance, and the use of PIFA, which is an air- and moisture-stable promoter. The mechanism studies showed that the reaction may proceed through a halonium ion species-mediated halogenation-elimination-halogenation stepwise process.
2. Novel zinc(II)-curcumin molecular probes bearing berberine and jatrorrhizine derivatives as potential mitochondria-targeting anti-neoplastic drugs
Shu-Hua Zhang, Zhen-Feng Wang, Haijun Tan Eur J Med Chem. 2022 Dec 5;243:114736. doi: 10.1016/j.ejmech.2022.114736. Epub 2022 Sep 3.
Berberine and jatrorrhizine are major bioactive components that are emerging as potential anti-cancer drugs. However, no zinc(II) - berberine/jatrorrhizine - curcumin compounds have been reported in the literature to date. Therefore, the molecular mechanisms associated with their cytotoxicity remain unexplored. To investigate the potential mitochondria-targeting ability, anti-neoplastic activity, and utility in cell imaging of berberine and jatrorrhizine derivates, four novel zinc(II) complexes, [Zn(Ber)(H2O)Cl2] (Zn(Ber)), [Zn(Ber)(Cur)Cl] (Zn(CurBer)), [Zn(Jat)(H2O)Cl2] (Zn(Jat)), and [Zn(Jat)(Cur)Cl] (Zn(CurJat)) bearing the berberine-derived ligand 2,2,2-trifluoroacetate 10-methoxy-9-((9-((2-(pyridin-2-yl)ethyl)amino)nonyl)oxy) -5,6-dihydro- [1,3]dioxolo[4,5-g]isoquinolino [(Torre et al., 2015; de Ruijter et al., 2020) 3,23,2-a]isoquinolin-7-ium (Ber), the jatrorrhizine-derived ligand 2,2,2-trifluoroacetate 2,9,10-trimethoxy-3-((9- ((2-(pyridin-2-yl)ethyl)amino)nonyl)oxy)-5,6-dihydroisoquinolino [(Torre et al., 2015; de Ruijter et al., 2020) 3,23,2-a]isoquinolin-7-ium (Jat), and/or curcumin (H-Cur) were first synthesised in this study. Zn(Ber), Zn(CurBer), Zn(Jat), and Zn(CurJat) showed higher cytotoxicity against human MCF-7 (breast adenocarcinoma) cells than did cisplatin, with IC50 values ranging from 0.21 to 4.45 μM. The anti-neoplastic activities of the zinc(II) - berberine/jatrorrhizine - curcumin complexes were in the following order: Zn(CurBer) > Zn(CurJat) > Zn(Ber) > Zn(Jat) > cisplatin > H-Cur > Ber > Jat > ZnCl2. Among these, Zn(CurBer) displayed the highest cytotoxicity (0.21 ± 0.06 μM). Furthermore, mechanistic investigations revealed that Zn(CurBer) and Zn(CurJat) could accumulate in the mitochondria, exhibit red fluorescence, and trigger mitophagy and apoptosis. In vivo anti-cancer evaluations also suggested that Zn(CurBer) inhibited MCF-7 xenograft tumour growth more effectively than cisplatin and Zn(CurJat). This is the first report describing the synthesis of zinc(II) - berberine/jatrorrhizine - curcumin complexes and their potential use as molecular probes and mitochondria-targeting anti-neoplastic drugs.
3. An Ornithine-Free Gramicidin S Analogue Using Norleucine, Cyclo(Val-Nle-Leu-D-Phe-Pro)2, Forms Helically Aligned β-Sheets
Akiko Asano, Chisato Minami, Shiori Matsuoka, Takuma Kato, Mitsunobu Doi Chem Pharm Bull (Tokyo). 2021;69(11):1097-1103. doi: 10.1248/cpb.c21-00548.
The structure of an ornithine (Orn)-free Gramicidin S (GS) analogue, cyclo(Val-Nle-Leu-D-Phe-Pro)2 (NGS), was studied. Its circular dichroism (CD) spectrum showed that NGS has a structure similar to GS, though the value of [θ] indicated smaller β-turn and sheet populations. This is probably because the Nle side chain could not form intramolecular hydrogen bonds stabilizing the sheet structure. The chemical shift perturbation of αH and JNH-αH were similar in GS and NGS. Three independent NGS molecules formed intramolecular β-sheet structures in crystal. The turn structures of D-Phe-Pro moieties were classed as type II' β-turns, but one part was unclassed. The molecules were arranged in a twisting manner, which resulted in the formation of a helical sheet. Similar structural characteristics were observed previously in a Leu-type, Orn-free GS analogue and in GS trifluoroacetic acid salt.
