2,6,16-Kauranetriol 2-O-beta-D-allopyranoside

Synthesis, Cytotoxic and Anti-proliferative Activity of Novel Thiophene, Thieno[2,3-b]pyridine and Pyran Derivatives Derived from 4,5,6,7-tetrahydrobenzo[b]thiophene Derivative.[Pubmed:28380235]

Acta Chim Slov. 2017 Mac;64(1):117-128.

Novel tetrahydrobenzo[b]thienopyrole derivatives are synthesized from 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene (1) through its reaction with alpha-chloroacetone to give the corresponding N-alkyl derivative 3. Compound 3 undergoes ready cyclization in sodium ethoxide solution to give the tetrahydrobenzo[b]thienopyrrole 4. The latter compound 4 is used as the key starting material for the synthesis of thiophene, thieno[2,3-b]pyridine and pyran derivatives. The cytotoxicity of the synthesized products towards the human cancer cell lines namely gastric cancer (NUGC), colon cancer (DLD-1), liver cancer (HA22T and HEPG-2), breast cancer (MCF-7), nasopharyngeal carcinoma (HONE-1) and normal fibroblast (WI-38) cell lines are measured. Compounds 4, 7a, 7b, 8a, 8b, 10c, 10d, 10f, 12a, 12b, 14b and 15b exhibit the optimal cytotoxic effect against cancer cell lines. Compounds 7b and 14b show the maximum inhibitory effect and these are much higher than the reference CHS-828 (pyridyl cyanoguanidine). On the other hand, the anti-proliferative evaluations of these compounds with high potency against the cancer cell lines L1210, Molt4/C8, CEM, K562, K562/4 and HCT116 show that compounds 7b and 8b give IC50's against Molt4/C8 and CEM cell lines higher than that of the reference, doxorubicin.

Structural and Functional State of Erythrocyte Membranes in Mice at Different Stages of Experimental Parkinson's Disease Induced by Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP).[Pubmed:28382410]

Bull Exp Biol Med. 2017 Mar;162(5):597-601.

We studied some structural and functional parameters of erythrocyte membranes in mice at the late presymptomatic and early symptomatic stages of experimental Parkinson's disease induced by administration of MPTP (hemolysis, microviscosity of different regions of the lipid bilayer, LPO intensity, activity of antioxidant enzymes, and kinetic properties of acetylcholinesterase). At the presymptomatic stage, significant deviations of the studied parameters from the normal were observed; they were similar in direction and magnitude to those in humans with Parkinson's disease. At the early symptomatic stage, most parameters tended to normal. Microviscosity of bulk lipids increased at the presymptomatic stage and decreased after appearance of clinical symptoms. This dynamics probably reflects activation of compensatory mechanisms aimed at inhibition of oxidative stress triggered by the development of the pathological process.

Dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines: Topoisomerase I and IIalpha dual inhibitors with DNA non-intercalative catalytic activity.[Pubmed:28384547]

Eur J Med Chem. 2017 Jun 16;133:69-84.

With the aim to develop novel antiproliferative agents, a new series of eighteen dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines were systematically designed, prepared, and investigated for their topoisomerase (topo) I and IIalpha inhibitory properties and antiproliferative effect in three different human cancer cell lines (HCT15, T47D, and HeLa). Compounds 22-30 which possess a meta- or para-phenol on 2-, or 6-position of central pyridine ring showed significant dual topo I and topo IIalpha inhibitory activities with strong antiproliferative activities against all the tested human cancer cell lines. However, compounds 13-21 which possess an ortho-phenol on 2-, or 6-position of central pyridine ring did not show significant topo I and topo IIalpha inhibitory activities but displayed moderate antiproliferative activities against all the tested human cancer cell lines. Compound 23 exhibited the highest antiproliferative potency as much as 348.5 and 105 times compared to etoposide and camptothecin, respectively, in T47D cancer cell line. The structure-activity relationship study revealed that the para position of a hydroxyl group at 2-and 6-phenyl ring and chlorine atom at the para position of 4-phenyl ring of the central pyridine exhibited the most significant topo I and topo IIalpha inhibition, which might indicate introduction of the chlorine atom at the phenyl ring of 4-pyridine have an important role as dual inhibitors of topo I and topo IIalpha. Compound 30 which showed the most potent dual topo I and topo IIalpha inhibition with strong antiproliferative activity in T47D cell line was selected to perform further study on the mechanism of action, which revealed that compound 30 functions as a potent DNA non-intercalative catalytic topo I and IIalpha dual inhibitor.

A Novel Methodology for Synthesis of 1,5,6-Trisubstituted 2(1H)-Pyrazinones of Biological Interest.[Pubmed:28381677]

Chem Pharm Bull (Tokyo). 2017;65(4):365-372.

In this report, we describe a new method for the synthesis of densely functionalized 2(1H)-pyrazinones. Treatment of mesoionic 1,3-oxazolium-5-olates with carbanions derived from activated methylene isocyanides (p-toluenesulfonylmethyl isocyanide (TosMIC) and ethyl isocyanoacetate) causes a novel ring transformation affording 2(1H)-pyrazinones in moderate to high yields. The cytotoxicity and antibacterial activity of some of the obtained products were studied and some of the products exhibited tumor-specific cytotoxicity.