Discovery of new 1,4-disubstituted 1,2,3-triazoles: in silico ADME profiling, molecular docking and biological evaluation studies

被引:28
作者
Sahin, Irfan [1 ]
Cesme, Mustafa [1 ]
Yuce, Neslihan [2 ]
Tumer, Ferhan [1 ]
机构
[1] Kahramanmaras Sutcu Imam Univ, Fac Art & Sci, Dept Chem, TR-46040 Kahramanmaras, Turkey
[2] Ataturk Univ, Dept Med Biochem, Fac Med, Erzurum, Turkey
关键词
Triazoles; anticancer; antioxidant activity; alpha-amylase inhibition; in silico; molecular docking; ADME; ANTIOXIDANT ACTIVITY; ANTIMICROBIAL ACTIVITY; DERIVATIVES DESIGN; INHIBITORS; ANTICANCER; ACID;
D O I
10.1080/07391102.2022.2025905
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In this work, eight new 1,2,3-triazoles (6a-h) were synthesized from acetylenes' "click" reaction with p-substituted azide derivatives. The structures of the compounds were characterized using standard analytical and spectroscopic methods (elemental analysis, FT-IR, H-1(C-13)NMR). The anticancer, antioxidant, alpha-amylase, ADME, molecular docking studies of synthesized triazoles were investigated. According to alpha -amylase enzyme inhibition results, all compounds except 6c (IC50: 2299 mu g/mL) were found to have a higher IC50 value than the standard drug acarbose (IC50: 891 mu g/mL). Compound 6g (IC50: 68 mu g/mL) exhibited 13 times higher activity than standard acarbose. All compounds, except 6e, have been shown to have greater DPPH radical scavenging capabilities than BHT and beta-carotene standards. According to ABTS radical scavenging studies, all compounds showed higher scavenging activity than ascorbic acid and Trolox. To determine the anticancer activity of the synthesized compounds, they were screened against the Hela cell line, and the results were compared with standard cisplatin (IC50: 16.30 mu g/mL). Compound 6a (IC50: 49.03 mu g/mL) was determined to have moderate activity relative to cisplatin. The compounds were examined comprehensively for ADME characteristics and did not violate any drug-likeness rule. ADME data showed that all physicochemical and pharmacological parameters of the compounds remained within defined limits as specified in Lipinski's rules (RO5) and put forth a high bioavailability profile. The molecular docking findings show that all molecules have a high affinity by exhibiting polar and apolar contact with essential residues in the binding pocket of alpha-amylase.
引用
收藏
页码:1988 / 2001
页数:14
相关论文
共 44 条
[31]   Computational study of molecular electrostatic potential, docking and dynamics simulations of gallic acid derivatives as ABL inhibitors [J].
Raghi, K. R. ;
Sherin, D. R. ;
Saumya, M. J. ;
Arun, P. S. ;
Sobha, V. N. ;
Manojkumar, T. K. .
COMPUTATIONAL BIOLOGY AND CHEMISTRY, 2018, 74 :239-246
[32]   A review on diverse heterocyclic compounds as the privileged scaffolds in non-steroidal aromatase inhibitors [J].
Rani, Sudesh ;
Raheja, Konpal ;
Luxami, Vijay ;
Paul, Kamaldeep .
BIOORGANIC CHEMISTRY, 2021, 113
[33]   Antioxidant activity applying an improved ABTS radical cation decolorization assay [J].
Re, R ;
Pellegrini, N ;
Proteggente, A ;
Pannala, A ;
Yang, M ;
Rice-Evans, C .
FREE RADICAL BIOLOGY AND MEDICINE, 1999, 26 (9-10) :1231-1237
[34]   Design and synthesis of 1,4-disubstituted 1,2,3-triazoles: Biological evaluation, in silico molecular docking and ADME screening [J].
Sahin, Irfan ;
Cesme, Mustafa ;
Ozgeris, Fatma Betul ;
Gungor, Ozge ;
Tumer, Ferhan .
JOURNAL OF MOLECULAR STRUCTURE, 2022, 1247
[35]   Synthesis, Characterization, and Antioxidant and Anticancer Activity of 1,4-Disubstituted 1,2,3-triazoles [J].
Sahin, Irfan ;
Ozgeris, Fatma Betul ;
Kose, Muhammet ;
Bakan, Ebubekir ;
Tumer, Ferhan .
JOURNAL OF MOLECULAR STRUCTURE, 2021, 1232
[36]   In silico fight against novel coronavirus by finding chromone derivatives as inhibitor of coronavirus main proteases enzyme [J].
Sepay, Nayim ;
Sepay, Nadir ;
Al Hoque, Ashique ;
Mondal, Rina ;
Halder, Umesh Chandra ;
Muddassir, Mohd .
STRUCTURAL CHEMISTRY, 2020, 31 (05) :1831-1840
[37]   Effect of geraniol against arecoline induced toxicity in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ) Bg9 [J].
Shakya, Barkha ;
Shakya, Sonam ;
Siddique, Yasir Hasan .
TOXICOLOGY MECHANISMS AND METHODS, 2019, 29 (03) :187-202
[38]   Charge transfer complex based real-time colorimetric chemosensor for rapid recognition of dinitrobenzene and discriminative detection of Fe2+ ions in aqueous media and human hemoglobin [J].
Shakya, Sonam ;
Khan, Ishaat M. ;
Ahmad, Musheer .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY, 2020, 392 (392)
[39]  
Sulaiman M., 2020, Journal of the Turkish Chemical Society Section A: Chemistry, V7, P481, DOI [10.18596/jotcsa.692113, DOI 10.18596/JOTCSA.692113]
[40]   Design, Synthesis, SAR and Molecular Modeling Studies of Novel Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives as Highly Potent Antimicrobial Agents [J].
Tahtaci, Hakan ;
Karacik, Hatice ;
Ece, Abdulilah ;
Er, Mustafa ;
Seker, Mine Gul .
MOLECULAR INFORMATICS, 2018, 37 (03)