Paraoxonase 1 (PON1), an esterase linked to high-density lipoprotein (HDL), is known to have strong antioxidant and anti-cardiovascular properties. In this study, eleven acetohydrazide-based sulfonamide derivatives were synthesized. All compounds were characterized by appropriate spectroscopic techniques and elemental analyses. To better understand the inhibitory properties of the new sulfonamide derivatives, their in vitro effects on purified PON1 enzyme activity were studied. For this purpose, PON1 was purified from human serum using simple chromatographic methods. In the experimental study, the novel compounds were found to be potent inhibitors of paraoxonase 1. The mode of binding to the enzyme, for the relatively active compounds, was investigated through molecular docking. The most active compound N'-(naphthalen-2ylsulfonyl)-2-(2-oxo-1,3-benzothiazol-3(2H)-yl)acetohydrazide demonstrated the highest interaction with the enzyme. Furthermore, the electrochemical properties of these compounds were assessed through DFT (density functional theory) analysis. N'-(naphthalen-2-ylsulfonyl)-2-(2-oxo-1,3-benzothiazol-3(2H)-yl)acetohydrazide is anticipated to have the highest potential to take part in electron exchanges whereas N'-[(4fluorophenyl)sulfonyl]-2-(2-oxo-1,3-benzoxazol-3(2H)yl)acetohydrazide is expected to have the highest chemical stability.

In this study, nine new benzothiazolone derivatives (6 a–i) were designed and synthesized to identify potent cholinesterase inhibitors. The compounds were tested in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and found to be selective to BChE. Compound 6 f proved the most potent derivative (IC50=12.25±0.23 μM) against BChE and was identified as a mixed‐type inhibitor with a Ki value of 4.45±0.35 μM according to the kinetic studies. Molecular modelling suggested that the derivatives were druglike and non‐PAINS. Compound 6 f showed good fit in BChE active site interacting with the key sites important for enzyme activity according to the molecular docking study.

Amaç: Kanser; ülkemizde ve dünyada öldürücülüğü yüksek olarak karşımıza çıkan ciddi sağlık sorunlarından biridir. İkinci sıklıkta görülen kanser türü olan meme kanseri kadınlarda en fazla ölüm nedenidir. Kanser hücresinin oluşum mekanizmalarının aydınlatılmasıyla, ilaç tedavilerinde bir çok yenilikçi yaklaşım keşfedilmiştir. Yenilikçi yaklaşımlardan biri de siklin bağımlı kinaz 4/6 inhibisyonudur. Bu derlemede siklin bağımlı kinaz 4/6 hakkında genel bilgiler verilerek, inhibitörlerinin avantaj ve dezantajları üzerinde durulmuştur.Sonuç ve Tartışma: Östrojen reseptörü pozitif ve insan epidermal büyüme faktör reseptörü 2 negatif meme kanserlerinde, endokrin tedavilere direncin gelişmesi tedavi sürecini kısıtlayan bir unsurdur. Retinoblastoma proteini pozitif meme kanserlerinde endokrin direncin üstesinden gelmek ve kanserli hücrenin mitoz kontrol noktasında durdurulması hedeflenerek siklin bağımlı kinaz 4/6 inhibisyon yolağı keşfedilmiştir. Siklin bağımlı kinaz 4 / 6 inhibitörlerinin endokrin tedaviyle kombinasyonuyla kanser terapisinde ümit verici sonuçlar elde edilmiştir.

Thirteen benzothiazolone derivatives (M1–M13) were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs) and monoamine oxidases (MAOs). All the compounds inhibited ChEs more effectively than MAOs. In addition, most of the compounds showed higher inhibitory activities against butyrylcholinesterase (BChE) than acetylcholinesterase (AChE). Compound M13 most potently inhibited BChE with an IC50 value of 1.21 μM, followed by M2 (IC50 = 1.38 μM). Compound M2 had a higher selectivity index (SI) value for BChE over AChE (28.99) than M13 (4.16). The 6-methoxy indole group of M13 was expected to have a greater effect on BChE inhibitory activity than the other groups. Kinetics and reversibility tests showed that M13 was a reversible noncompetitive BChE inhibitor with a Ki value of 1.14 ± 0.21 μM. In a docking simulation, M13 is predicted to form a hydrogen bond with the backbone carbonyl group of Ser287 of BChE through its methoxy indole moiety and π−π interactions between its benzothiazolone group and the side chain of Trp82 with the five-membered pyrrole ring and with the six-membered benzene ring. From these results, it is suggested that M13 is a BChE inhibitor and a potential candidate agent for the treatment of Alzheimer’s disease.