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ŞENOL, HALIL

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HALIL
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ŞENOL
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    PublicationOpen Access
    Synthesis and Evaluation of Quinazolin-4(3H)-one Derivatives as Multitarget Metabolic Enzyme Inhibitors: A Biochemistry-Oriented Drug Design
    (2023-07-01) Tokalı F. S.; Taslimi P.; Sadeghi M.; Şenol H.; ŞENOL, HALIL
    In this study, imines bearing quinazolin-4(3H)-one were synthesized and their inhibitory properties were investigated against some metabolic enzymes including Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), & alpha;-Glycosidase (& alpha;-Gly), and human Carbonic Anhydrase I-II (hCA I-II). All compounds had inhibitory strength with K-i values in the range of 38.55 & PLUSMN;4.08-159.05 & PLUSMN;10.68 nM and 41.04 & PLUSMN;6.73-177.12 & PLUSMN;8.06 nM against hCA I and hCA-II, respectively in comparison to the standard acetazolamide (AZA) K-i=125.15 & PLUSMN;0.78 nM (for hCA-I) and K-i=148.75 & PLUSMN;0.92 nM (for hCA-II). The compounds showed potent inhibitory activity against & alpha;-Gly enzyme with IC50 value 0.34-2.28 nM (standard inhibitor acarbose (ACR): 3.18 nM). Also, these analogs had potent inhibitory strength with K-i values in the range of 4.20 & PLUSMN;0.15-26.10 & PLUSMN;2.36 nM against AChE and 1.22 & PLUSMN;0.05-16.09 & PLUSMN;0.88 nM against BChE in comparison to the standard tacrine (TAC) K-i=37.62 & PLUSMN;6.86 nM (for AChE) and K-i=26.75 & PLUSMN;5.79 nM (for BChE). Additionally, the molecular docking and molecular dynamics simulation study was carried out for the determination of ligand-enzyme interactions. The docking scores of the most active compound were calculated as -7.31, -7.59, -6.66, -6.93 and -7.11 kcal/mol for AChE, BChE, hCA I, hCA II, and & alpha;-Gly, respectively.
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    PublicationOpen Access
    Synthesis and anticancer activity of novel derivatives of α,β‐unsaturated ketones based on oleanolic acid: in vitro and in silico studies against prostate cancer cells
    (2023-08-01) Şenol H.; Ghaffari-Moghaddam M.; Bulut Ş.; Akbaş F.; Köse A.; Topçu G.; ŞENOL, HALIL; AKBAŞ, FAHRİ; TOPÇU, GÜLAÇTI
    Herein, new derivatives of α,β-unsaturated ketones based on oleanolic acid (4 a-i) were designed, synthesized, characterized, and tested against human prostate cancer (PC3). According to the in vitro cytotoxic study, title compounds (4 a-i) showed significantly lower toxicity toward healthy cells (HUVEC) in comparison with the reference drug doxorubicin. The compounds with the lowest IC50 values on PC3 cell lines were 4 b (7.785 μM), 4 c (8.869 μM), and 4 e (8.765 μM). The results of the ADME calculations showed that the drug-likeness parameters were within the defined ranges according to Lipinski's and Jorgensen's rules. For the most potent compounds 4 b, 4 c, and 4 e, a molecular docking analysis using the induced fit docking (IFD) protocol was performed against three protein targets (PARP, PI3K, and mTOR). Based on the IFD scores, compound 4 b had the highest calculated affinity for PARP1, while compound 4 c had higher affinities for mTOR and PI3K. The MM-GBSA calculations showed that the most potent compounds had high binding affinities and formed stable complexes with the protein targets. Finally, a 50 ns molecular dynamics simulation was performed to study the behavior of protein target complexes under in silico physiological conditions.
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    PublicationOpen Access
    3-Amino-thiophene-2-carbohydrazide Derivatives as Anti Colon Cancer Agents: Synthesis, Characterization, In-Silico and In-Vitro Biological Activity Studies
    (2023-10-01) Şenol H.; Çakır F.; ŞENOL, HALIL
    In this study, starting from 3-amino-thiophene-2-carboxylic acid methyl ester, eighteen new arylidenehydrazide derivatives (4–21) were synthesized. To determine cytotoxic activity of target compounds they were tested against human colon cancer and human umbilical vein endothelial cell lines. To determine prospective inhibition mechanism, binding affinity and complex stability molecular docking and molecular dynamics studies were carried out on transforming growth factor beta-2 (TGFβ2) and vascular endothelial growth factor receptor 2 (VEGFR2) proteins. According to the biological activity studies compounds (E)-2,4-dichloro-N-(2-(2-(4-fluorobenzylidene)hydrazine-1-carbonyl)thiophen-3-yl)benzamide (11) was found as the highest selective and active compound. Anti-cancer activity results compared to reference drugs doxorubicin and gefitinib. Most active compound was found as 7-fold and 4-fold more selective than doxorubicin and gefitinib, respectively. The detailed in vitro and in silico biological activity studies revealed that related compound demonstrated strong and selective anti-colon cancer effect and also it has promising inhibitory effects on TGFβ2 and VEGFR2. As a result, this compound is a promising candidate for further exploration and development in the field of colon cancer treatment.