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Synthesis and structure-activity relationship of elastase inhibiting novel ethylated thiazole-triazole acetamide hybrids: Mechanistic insights through kinetics and computational contemplations.
Bioorg Chem. 2019 05; 86:197-209.BC

Abstract

Keeping in mind the pharmacological importance of 2-aminothiazole and 1,2,4-triazole heterocyclic moieties, a series of novel ethylated bi-heterocyclic acetamide hybrids, 9a-p, was synthesized in a multi-step protocol. The structures of newly synthesized compounds were characterized by 1H NMR, 13C NMR, IR and EI-MS spectral studies. The inhibitory effects of these bi-heterocyclic acetamides (9a-n) were evaluated against elastase and all these molecules were identified as potent inhibitors relative to the standard used. The Kinetics mechanism was analyzed by Lineweaver-Burk plots which revealed that, 9h, inhibited elastase competitively by forming an enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.9 µM. The computational study was articulate with the experimental results and these ligands unveiled good binding energy values (kcal/mol). So, these molecules can be considered as promising medicinal scaffolds for the treatment of skin melanoma, wrinkle formation, uneven pigmentation, and solar elastosis.

Authors+Show Affiliations

Department of Chemistry, Government College University, Lahore 54000, Pakistan.Department of Chemistry, Government College University, Lahore 54000, Pakistan; College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju 32588, South Korea. Electronic address: abbasi@gcu.edu.pk.Department of Chemistry, Government College University, Lahore 54000, Pakistan.Department of Chemistry, Government College University, Lahore 54000, Pakistan.College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju 32588, South Korea.College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju 32588, South Korea.Faculty of Pharmacy and Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Level 9, FF3, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.Department of Chemistry, Government College University, Lahore 54000, Pakistan. Electronic address: dnalove@kongju.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

30711702

Citation

Butt, Abdul Rehman Sadiq, et al. "Synthesis and Structure-activity Relationship of Elastase Inhibiting Novel Ethylated Thiazole-triazole Acetamide Hybrids: Mechanistic Insights Through Kinetics and Computational Contemplations." Bioorganic Chemistry, vol. 86, 2019, pp. 197-209.
Butt ARS, Abbasi MA, Aziz-Ur-Rehman , et al. Synthesis and structure-activity relationship of elastase inhibiting novel ethylated thiazole-triazole acetamide hybrids: Mechanistic insights through kinetics and computational contemplations. Bioorg Chem. 2019;86:197-209.
Butt, A. R. S., Abbasi, M. A., Aziz-Ur-Rehman, ., Siddiqui, S. Z., Hassan, M., Raza, H., Shah, S. A. A., & Seo, S. Y. (2019). Synthesis and structure-activity relationship of elastase inhibiting novel ethylated thiazole-triazole acetamide hybrids: Mechanistic insights through kinetics and computational contemplations. Bioorganic Chemistry, 86, 197-209. https://doi.org/10.1016/j.bioorg.2019.01.040
Butt ARS, et al. Synthesis and Structure-activity Relationship of Elastase Inhibiting Novel Ethylated Thiazole-triazole Acetamide Hybrids: Mechanistic Insights Through Kinetics and Computational Contemplations. Bioorg Chem. 2019;86:197-209. PubMed PMID: 30711702.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and structure-activity relationship of elastase inhibiting novel ethylated thiazole-triazole acetamide hybrids: Mechanistic insights through kinetics and computational contemplations. AU - Butt,Abdul Rehman Sadiq, AU - Abbasi,Muhammad Athar, AU - Aziz-Ur-Rehman,, AU - Siddiqui,Sabahat Zahra, AU - Hassan,Mubashir, AU - Raza,Hussain, AU - Shah,Syed Adnan Ali, AU - Seo,Sung-Yum, Y1 - 2019/01/28/ PY - 2018/11/07/received PY - 2019/01/09/revised PY - 2019/01/21/accepted PY - 2019/2/4/pubmed PY - 2020/4/1/medline PY - 2019/2/4/entrez KW - 1,2,4-Triazole KW - 1,3-Thiazole KW - Acetamides KW - Elastase KW - Kinetics KW - Molecular docking SP - 197 EP - 209 JF - Bioorganic chemistry JO - Bioorg. Chem. VL - 86 N2 - Keeping in mind the pharmacological importance of 2-aminothiazole and 1,2,4-triazole heterocyclic moieties, a series of novel ethylated bi-heterocyclic acetamide hybrids, 9a-p, was synthesized in a multi-step protocol. The structures of newly synthesized compounds were characterized by 1H NMR, 13C NMR, IR and EI-MS spectral studies. The inhibitory effects of these bi-heterocyclic acetamides (9a-n) were evaluated against elastase and all these molecules were identified as potent inhibitors relative to the standard used. The Kinetics mechanism was analyzed by Lineweaver-Burk plots which revealed that, 9h, inhibited elastase competitively by forming an enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.9 µM. The computational study was articulate with the experimental results and these ligands unveiled good binding energy values (kcal/mol). So, these molecules can be considered as promising medicinal scaffolds for the treatment of skin melanoma, wrinkle formation, uneven pigmentation, and solar elastosis. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/30711702/Synthesis_and_structure_activity_relationship_of_elastase_inhibiting_novel_ethylated_thiazole_triazole_acetamide_hybrids:_Mechanistic_insights_through_kinetics_and_computational_contemplations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(18)31279-3 DB - PRIME DP - Unbound Medicine ER -