BACKGROUND/AIM: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. MATERIALS AND METHODS: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay. RESULTS: Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 μM). Thioridazine was the most potent among the three phenothiazines. CONCLUSION: Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, therefore, their use as adjuvants in cancer may be considered as a potential drug repurposing strategy. Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Alzheimer's disease (AD) is multifactorial disease characterized by the accumulation of abnormal extracellular deposits of amyloid-beta (Aβ) peptide, and intracellular neurofibrillary tangles (NFTs), along with dramatic neuronal death and decreased levels of choline acetyltransferase. Given the limited therapeutic success of available drugs, it is urgent to explore all the opportunities available to combat this illness. Among them, the discovery of new heterocyclic scaffolds binding different receptors involved in AD should offer structural diversity and new therapeutic solutions. In this context, this work describes new triazolopyridopyrimidine easily prepared in good yields showing anticholinesterase inhibition and strong antioxidant power, particularly the most balanced: 6-amino-5-(4-methoxyphenyl)-2-phenyl-[1,2,4]triazolo[1',5':1,6] pyrido[2,3-d]pyrimidine-4-carbonitrile(3c) with IC50 equal to 1.32 μM against AChE and oxygen radical absorbance capacity (ORAC) value equal to 4.01 Trolox equivalents (TE); thus representing a new and very promising hit-triazolopyridopyrimidine for AD therapy.

Currently there is great interest in exploitation of agrofood by-products, such as those from legumes, as source of bioactive ingredients. To that aim, characterization of cyclitol and sugar composition of pods and seeds from different legume species has been carried out. A green Microwave Assisted Extraction (MAE) method was optimized for extraction of bioactive inositols, and both pod and seed yields were compared with those obtained by conventional reflux extraction. A subsequent Saccharomyces cerevisiae treatment was also evaluated for removal of interfering coextracted sugars. myo-Inositol was present in all legume pods and seeds and galactinol in most seeds. chiro-Inositol was found in soybean and basul, whereas outstanding pinitol concentrations were only detected in soybean. The optimized MAE method provided extracts rich in pinitol from soybean pods (41.5–58.0 mg g−1) and seeds (5.3–7.5 mg g−1). Removal of 97\% of interfering sugars in MAE soybean pod extracts was achieved by yeast treatment. © 2020 Elsevier Ltd

Pyridine-substituted alkylidenecyclopropanes (Py-ACPs) react with gold(III) salts under mild reaction conditions through an unprecedented, proximal ring-opening pathway, to generate highly appealing, catalytically active pyridine alkenyl [C^N]-gold(III) species. Mechanistic studies reveal that the activation of the C−C bond of the ACP takes place through an unusual concerted, σ-bond metathesis type-process. © 2020 Wiley-VCH GmbH

A Pd catalyst made from a Pd(0) source and a bulky biaryl phosphine ligand promotes highly efficient intramolecular (3 + 2) heterocycloadditions between alkylidenecyclopropanes (ACPs) and carbonyls. The annulations provide a straightforward access to fused polycyclic systems featuring β-methylene tetrahydrofuran moieties. DFT data support a pallada-ene process and shed light on the critical role of hemilabile interactions between the Pd center and the bulky biaryl phosphine. Significantly, these Pd(0) catalysts are also effective for promoting intermolecular formal cycloadditions between ACPs and trifluoromethyl ketones, thus providing for a direct entry to chiral tetrahydrofuran moieties (THFs) bearing trifluoromethyl-substituted carbons. © 2020 American Chemical Society.

3-n-Butylphthalide (NBP) as well as its derivatives and analogues (NBPs), in racemic or enantiomerically pure forms, possess potent and diverse pharmacological properties and have shown a great potential therapeutic interest for many human conditions, especially for cerebral ischemia. This Perspective outlines the synthesis and therapeutic applications of NBPs. © 2020 American Chemical Society. All rights reserved.

The synthesis of enantiomerically pure Ir(III) complexes with one or two BODIPY moieties has been achieved through the enantioselective C–H insertion from homochiral triazolium salts, containing a sulfoxide functionality in their structures. These homochiral salts were prepared by the sequential Cu-catalyzed alkyne-azide cycloaddition (CuAAC) of an azide and one alkynyl sulfoxide, followed by a Suzuki coupling in the preformed triazole with a BODIPY containing aryl boronic acid, followed by methylation of the N3-triazole nitrogen. The configuration at the metal in these chiral complexes was established by using a combination of CD and X-ray diffraction techniques. The optical properties of these complexes were thoroughly studied using spectroscopic (absorption and fluorescence) and computational (TD-DFT and DFT) methods. The fluorescence of complexes with the BODIPY attached to the sulfoxide moiety (including the two BODIPYs-based complex) was quenched upon introduction of the Ir(III) fragment, most likely due to an a-PET mechanism. On the contrary, the fluorescence of Ir(III) complexes with the BODIPY attached to the triazolium ring remains unquenched. © 2020 Wiley-VCH GmbH

The antimicrobial evaluation of twelve natural and hemisynthetic isopimarane diterpenes are reported. The compounds were evaluated against a panel of Gram-positive bacteria, including two methicillin-resistant Staphylococcus aureus (MRSA) strains and one vancomycin-resistant Enterococcus (VRE) strain. Only natural compounds 7,15-isopimaradien-19-ol (1) and 19-acetoxy-7,15-isopimaradien-3β-ol (6) showed promising results. Isopimarane (1) was the most active, showing MIC values between 6.76 µM against S. aureus (ATCC 43866) and 216.62 µM against E. faecalis (FFHB 427483) and E. flavescens (ATCC 49996). Compound (6) showed moderated activity against all tested microorganisms (MIC between value 22.54 and 45.07 µM). These compounds were found to be active against the methicillin-sensitive strains of S. aureus (CIP 106760 and FFHB 29593), showing MIC values of 13.55 (1) and 22.54 (6) µM. Both compounds were also active against vancomycin-resistant E. faecalis (ATCC 51299) (MIC values of 54.14 and 45.07 µM, respectively). In addition, the cytotoxicity of nine compounds 7,15-isopimaradien-3β,19-diol (2); mixture: 15-isopimarene-8β-isobutyryloxy-19-ol and 15-isopimarene-8β-butyryloxy-19-ol (3); 3β-acetoxy-7,15-isopimaradiene-19-ol (5); 19-acetoxy-7,15-isopimaradiene-3β-ol (6); 3β,19-diacetoxy-7,15-isopimaradiene (8); 15-isopimarene-8β,19-diol (9); 19-O-β-d-glucopyranoside-7,15-isopimaradiene (10); lagascatriol-16-O-β-d-glucopyranoside (11) and lagascatriol-16-O-α-d-mannopyranoside (12) was evaluated in the human breast cancer cell line MDA-MB-231. Isopimarane (2) was the only compound showing some cytotoxicity. The IC50 value of compound (2) was 15 µM, suggesting a mild antiproliferative activity against these breast cancer cells. © 2020 by the authors.