In vitro cytotoxic evaluation of a novel phosphinyl derivative of boldine.

2,9-Dimethoxymethylboldine (2), 2,9-dimethoxymethyl-3-bromoboldine (3) and 2,9-dimethoxymethyl-3-diphenylphosphinylboldine (4) have been synthesized in an effort to find compounds with potential pharmacological applications. The cytotoxic activities of the natural precursor 1 and these three derivatives have been measured as IC50 inhibitory growth. The diphenylphosphinyl derivative 4 showed a significant cytotoxic activity on two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC50 values of 55.5 and 62.7 [µM], respectively. These results suggest that the kind of structural modifications introduced to synthesize compound 4 represent a promising way to enhance the cytotoxic activity of boldine derivatives.

Water-soluble Ru(II)-anethole compounds with promising cytotoxicity toward the human gastric cancer cell line AGS.

AIMS: Ruthenium-based compounds exhibit critical biochemical properties making them suitable for diverse pharmacological applications. The aim of this work was to study the anticancer effects of three ruthenium complexes on a human gastric cancer cell line. MAIN METHODS: We synthetized three [Ru(η6-anethole)(en)X]PF6 complexes, where (en) is ethylenediamine and X is Cl (1), Br (2) or I (3), which were then evaluated by MTT assay, RT-qPCR and flow cytometry on the human gastric cancer cell line AGS. KEY FINDINGS: Compound 3 exhibited the highest cytotoxicity (IC50 = 11.27 ±â€¯1.08 µM) of the series, with an activity almost three-fold more potent than the commercial drug cisplatin, and also revealed a 4.5-fold less potent cytotoxicity in the human normal gastric cell line GES-1. The exchange of the halogen (Cl, Br or I) on the organometallic compound slightly alters its solubility in PBS and lipophilicity (expressed as Log P). Studies of gene expression revealed that compound 3 induces a significant overexpression of the pro-apoptotic genes Caspase-3, PUMA and DIABLO in the gastric cancer cell line AGS after 6 h. In contrast, only PUMA was significantly overexpressed in the normal gastric cell line GES-1. Compound 3 induced the activation of multiple caspases in AGS cells: a sign of apoptosis. Characterization via single-crystal X-ray diffraction for compound 3 confirmed the key structural features for this type of organometallic complexes. SIGNIFICANCE: Our data suggests that compound 3 may be an interesting anticancer molecule for the treatment of gastric cancer.

Oxaliplatin analogues with carboxy derivatives of boldine with enhanced antioxidant activity.

A new oxaliplatin analog [Pt(dach)(L5)] (1) was synthesized and characterized as a continuation of a study of the previously reported [Pt(dach)(L6)] (2), where dach = (1R,2R)-diaminocyclohexane, L5 = 3-carboxyboldine, and L6 = 3-carboxypredicentrine. Compounds 1 and 2 exhibited a substantially enhanced antioxidant activity compared to oxaliplatin (130 and 30 times for 1 and 13 and 4 times for 2 using the DPPH and FRAP assays, resp.). In addition, 1 and 2 exhibited cytotoxic activity in the same range as oxaliplatin toward the two human tumor cell lines (MCF-7 and HT-29) studied and two to four times lower activity in the human colon nontumor cell line (CCD-841). Preadministration of L5 or L6 to the colon tumor (HT-29) and the colon nontumor (CCD-841) cell lines prior to oxaliplatin addition increased the viability of the nontumor cell line to a greater extent than that of the tumor cell line.

Cytotoxic thiocarbamate derivatives of boldine.

Two new boldine derivatives: the 3-thiocarbamateboldine (3) and the 2,9-O,O-diacetyl-3-thiocarbamateboldine (4) have been synthesized and their cytotoxicity evaluated.