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Chalcones targeting neurodegenerative diseases have been known as attractive structures in drug design and discovery. In this study, phenothiazine-based chalcones as ChEs and MAOs inhibitors were designed and synthesizedviabase-catalyzed Claisen-Schmidt condensation, and chemical structures of the compounds were elucidated by NMRs and HRMS. Compounds3and9showed promising inhibition potency against AChE enzyme with IC(50)values of 0.221 mu M and 0.053 mu M while compound9displayed remarkable inhibition potency toward MAO-B enzyme with IC(50)value of 0.048 mu M. Compound9, as a dual-target inhibitor, selectively inhibited AChE and MAO-B enzymes. This promising behavior is an advantage for the compound since MAO-B and AChE inhibition have a role in Alzheimer's disease. Fused tricyclic ring systems such as phenothiazine incorporated with chalcone moiety being multitargeting ligands may help scientists for the rational design of novel lead compounds targeting neurodegenerative illnesses.

In this study, new 4-13-(aryl)-5-substitutedphenyl-4,5-dihydro-1H-pyrazole-1-yllbenzensulfonamides (19-36) were synthesized and evaluated their cytotoxic/anticancer and CA inhibitory effects. According to results obtained, the compounds 34 (4-[5-(2,3,4-trimethoxyphenyl)-3-(thiophen-2-yl)4,5-dihydro-1H-pyrazole-1-yl benzensulfonamide, Potency-Selectivity Expression (PSE) = 141) and 36 (44 543,4,5-trimethoxyphenyl)-3-( thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl benzensulfonamide, PSE = 54.5) were found the leader anticancer compounds with the highest PSE values. In CA inhibitory studies, the compounds 36 and 24 (4-[5-(3,4,5-trimethoxyphenyl) 3 (4 fluorophenyl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide) were found the leader CA inhibitors depending on selectivity ratios. The compound 36 was a selective inhibitor of hCA XII isoenzyme (hCA l/hCA XII = 1250 and hCA II/hCA XII = 224) while the compound 24 was a selective inhibitor of hCA IX isoenzyme (hCA l/hCA IX = 161 and hCA II/hCA IX = 177). The compounds 24, 34, and 36 can be considered to develop new anticancer drug candidates. (C) 2018 Elsevier Inc. All rights reserved., TUBITAK [2016-115S694], This work was supported by the TUBITAK (Project Number: 2016-115S694). Authors thank to Dr. Yusuf Ozkay and MSc. Serkan Levent (Anadolu University, Faculty of Pharmacy, Eskisehir, Turkey) for HRMS analysis and Ataturk University, Faculty of Science, Department of Chemistry for NMRs.

The compounds titled 1-(2,5/3,5-difluorophenyl)-3-(2,3/2,4/2,5/3,4-dimethoxyphenyl)-2-propen-1-ones (1-8) were synthesized via Claisen-Schmidt condensation under basic condition. The chemical structure of the compounds were identified using several spectroscopic techniques such as H-1 nuclear magnetic resonance (NMR), C-13 NMR, F-19 NMR, DEPT 90, DEPT 135, COSY, HMBC, and HMQC. Cytotoxic activities of the compounds were investigated towards several human tumour cell lines [gingival carcinoma (Ca9-22), oral squamous cell carcinoma derived from tongue (HSC-2)] and human normal oral cells [gingival fibroblasts (HGF), periodontal ligament fibroblasts (HPLF)]. Most of these compounds presented higher cytotoxicity than reference drug 5-fluorouracil while the compounds 7, [1-(3,5-difluorophenyl)-3-(2,5-dimethoxyphenyl)-2-propen-1-one)], and 2, [1-(2,5-difluorophenyl)-3-(2,4-dimethoxyphenyl)-2-propen-1-one], were presenting the best activity according to potency selectivity expression values. Type of cell death induced by compound 7 in both HSC-2 and Ca9-22 cells was investigated to understand mechanism of action of the compounds. The compound 7 produced cleaved products of PARP and caspase-3 were produced, suggesting the induction of apoptosis as a possible mechanism of action of the compounds characterized via activation of caspase-3 in both human oral squamous cell carcinomas., Ataturk University Research Found, Turkey [2015/078], This research work was supported by Ataturk University Research Found, Turkey (Project No: 2015/078). Gul HI thanks to Dr. Yusuf Ozkay (Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey) and MSc. Serkan Levent (Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey) for HRMS analyses.

The effects of isatin Mannich bases incorporating (1-[piperidin-1-yl (P1)/morpholin-4-yl (P2)/N-methylpiperazin-1-yl (P3)]methyl)-1H-indole-2,3-dione) moieties against human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoenzymes hCA I and hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes were evaluated. P1-P3 demonstrated impressive inhibition profiles against AChE and BChE and also inhibited both CAs at nanomolar level. These inhibitory effects were more powerful in all cases than the reference compounds used for all these enzymes. This study suggests that isatin Mannich bases P1-P3 are good candidate compounds especially for the development of new cholinesterase inhibitors since they were 2.2-5.9 times better inhibitors than clinically used drug Tacrine., Research Foundation of Agri Ibrahim Cecen University, Turkey [FEF.14.009], This study was supported by the Research Foundation of Agri Ibrahim Cecen University, Turkey, Project No: FEF.14.009.

Pyrazolines are reported with a broad range of bioactivities, excellent fluorescence properties and easy synthesis. But unfortunately, there is no or very limited information available about their pH sensor application. Additionally, there is a little information about “off-on-off” type of pH sensors in literature. To fulfill the gap in literature and try to find out new possible “off-on-off” pH sensor, in this study it was planned to investigate the changes in the photo-physical properties of four pyrazolines D1–D4, 4-(5-(3,4-dimethoxyphenyl)-3-(4-substitutedphenyl)-4,5-dihydro-1H-pyrazol-1-yl)benzene sulfonamide, in water and different pH (2, 4, 6, 8, 9, 10, 12) in which on phenyl was H (D1), F (D2), Cl (D3) and Br (D4). The compound D1 exhibited excellent fluorescence properties and high fluorescence quantum yields in water. When the compounds D2–D4 which have electron-withdrawing substituents F, Cl and Br in D2–D4, respectively, were considered, it was observed that fluorescence quenching occurred in the molecules in question due to increased intersystem crossing probability while D1 did not show fluorescence quenching. However, the photo-physical properties of the compounds D1–D4 displayed important changes as a function of pH. It follows from these important changes that the compounds D1–D4 have “off-on-off” type of fluorescent pH sensor properties based on intramolecular charge transfer (ICT). These results indicated that these pyrazoline derivatives would be able to act as an efficient “off-on-off” fluorescent pH sensor in biological, environmental and medical etc. areas.

Background: Although anticancer chemotherapeutics are available in markets, side effects related to the drugs in clinical use lead to researchers to investigate new drug candidates which are more safe, potent and selective than others. Chalcones are popular with their anticancer activities with the several reported mechanisms including inhibition of angiogenesis, inhibition of tubulin polymerization, and induction of apoptosis etc. Objective: This study was focused on to synthesize of 1-(2,4/2,6-difluorophenyl)-3-(2,3/2,4/2,5/3,4dimethoxyphenyl)- 2-propen-1-ones (1-8) and investigate their cytotoxic properties with possible mechanism of action. Method: The compounds were synthesized by Claisen-Schmidt condensation. The chemical structures were confirmed by H-1 NMR, C-13 NMR, DEPT, COSY, HMQC, HMBC, F-19 NMR and HRMS. In vitro cytotoxic effects of the compounds against human tumour cell lines [gingival carcinoma (Ca9-22), oral squamous cell carcinoma (HSC-2)] and human normal oral cells [gingival fibroblasts (HGF), periodontal ligament fibroblasts (HPLF)] were evaluated via MTT test. Results: All compounds had higher cytotoxicity than reference compound 5-Fluorouracil (5-FU). The compounds 3-7 had higher potency selectivity expression values (PSE) than 5-FU and PSE values of the compounds were over 100. All chalcone derivatives seem good candidates for further studies according to very remarkable and high PSE values. Conclusion: It was clearly demonstrated that compound 7 can induce early apoptosis at a concentration of 10 mu M and dose-dependent late apoptosis starting at 10 mu M. Compound 7 induced cleavage of the apoptosis marker PARP. The results indicate that new chalcones reported here can promote apoptosis in human tumour cell lines., Ataturk University Research Found, Turkey [2015/078]; JSPS KAKENHI [26861748], This work was supported by Ataturk University Research Found, Turkey (Grant Number 2015/078) and in part of JSPS KAKENHI (Grant Number 26861748). The authors are thankful to Dr. Hong Sheng (Meikai Univercity, Japan) for technical assistance, Dr. Yusuf Ozkay (Anadolu University, Turkey) for HRMS spectra and Ataturk University, Faculty of Science, Department of Organic Chemistry, Turkey for NMRs spectra.