Tags

Type your tag names separated by a space and hit enter

Substituted (E)-2-(2-benzylidenehydrazinyl)-4-methylthiazole-5-carboxylates as dual inhibitors of 15-lipoxygenase & carbonic anhydrase II: synthesis, biochemical evaluation and docking studies.
Biochem Biophys Res Commun. 2017 Jan 01; 482(1):176-181.BB

Abstract

15-Lipoxygenase (15-LOX) plays a major role in many inflammatory lung diseases including chronic obstructive pulmonary disease (COPD), asthma and chronic bronchitis. Over-expression of 15-LOX is related with some specific carcinomas including pancreatic, gastric and brain tumor. Similarly among different isozymes of carbonic anhydrase (CA), CA II is expressed in pancreatic, gastric carcinomas as well as in brain tumors. Therefore, novel potent inhibitors of both 15-LOX and CA II are required to explore the role of these enzymes further and to enable the drug discovery efforts. For this purpose, a series of benzyledinyl-hydrazinyl substituted thiazole derivatives were designed, synthesized and characterized by FTIR, 1H, &13C NMR spectroscopy. The derivatives were then evaluated for their potential to inhibit 15-LOX and bovine carbonic anhydrase II (bCA II). Most of these compounds showed excellent inhibitory potential for 15-LOX with an IC50 of 0.12 ± 0.002 to 0.69 ± 0.5 μM and showed moderate inhibition potency for bCA II with compound 5h (IC50 = 1.26 ± 0.24 μM) being the most active. The most potent compound 5a that emerged as a dual inhibitor of both enzymes, exhibiting 24 times greater selectivity for 15-LOX over bCA II. Compound 5a exhibited dual potent inhibitory activity against both 15-LOX and bCA II enzymes having IC50 values of 0.12 ± 0.002 and 2.93 ± 0.22 μM, respectively. Molecular docking studies of potent as well as dual inhibitors were also carried out to provide an insight into the binding site interactions.

Authors+Show Affiliations

Department of Chemistry, Quaid-i-Azam University, 45320, Islamabad, Pakistan. Electronic address: aamersaeed@yahoo.com.Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan.Department of Chemistry, Quaid-i-Azam University, 45320, Islamabad, Pakistan.Department of Chemistry, Quaid-i-Azam University, 45320, Islamabad, Pakistan.Department of Chemistry, Quaid-i-Azam University, 45320, Islamabad, Pakistan.Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan. Electronic address: drjamshed@ciit.net.pk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27836541

Citation

Saeed, Aamer, et al. "Substituted (E)-2-(2-benzylidenehydrazinyl)-4-methylthiazole-5-carboxylates as Dual Inhibitors of 15-lipoxygenase & Carbonic Anhydrase II: Synthesis, Biochemical Evaluation and Docking Studies." Biochemical and Biophysical Research Communications, vol. 482, no. 1, 2017, pp. 176-181.
Saeed A, Khan SU, Mahesar PA, et al. Substituted (E)-2-(2-benzylidenehydrazinyl)-4-methylthiazole-5-carboxylates as dual inhibitors of 15-lipoxygenase & carbonic anhydrase II: synthesis, biochemical evaluation and docking studies. Biochem Biophys Res Commun. 2017;482(1):176-181.
Saeed, A., Khan, S. U., Mahesar, P. A., Channar, P. A., Shabir, G., & Iqbal, J. (2017). Substituted (E)-2-(2-benzylidenehydrazinyl)-4-methylthiazole-5-carboxylates as dual inhibitors of 15-lipoxygenase & carbonic anhydrase II: synthesis, biochemical evaluation and docking studies. Biochemical and Biophysical Research Communications, 482(1), 176-181. https://doi.org/10.1016/j.bbrc.2016.11.028
Saeed A, et al. Substituted (E)-2-(2-benzylidenehydrazinyl)-4-methylthiazole-5-carboxylates as Dual Inhibitors of 15-lipoxygenase & Carbonic Anhydrase II: Synthesis, Biochemical Evaluation and Docking Studies. Biochem Biophys Res Commun. 2017 Jan 1;482(1):176-181. PubMed PMID: 27836541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Substituted (E)-2-(2-benzylidenehydrazinyl)-4-methylthiazole-5-carboxylates as dual inhibitors of 15-lipoxygenase & carbonic anhydrase II: synthesis, biochemical evaluation and docking studies. AU - Saeed,Aamer, AU - Khan,Shafi Ullah, AU - Mahesar,Parvez Ali, AU - Channar,Pervaiz Ali, AU - Shabir,Ghulam, AU - Iqbal,Jamshed, Y1 - 2016/11/09/ PY - 2016/11/01/received PY - 2016/11/06/accepted PY - 2016/11/12/pubmed PY - 2017/5/30/medline PY - 2016/11/13/entrez KW - 15-Lipoxygenase KW - Bovine carbonic anhydrase II KW - Docking studies KW - Thiazoles SP - 176 EP - 181 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 482 IS - 1 N2 - 15-Lipoxygenase (15-LOX) plays a major role in many inflammatory lung diseases including chronic obstructive pulmonary disease (COPD), asthma and chronic bronchitis. Over-expression of 15-LOX is related with some specific carcinomas including pancreatic, gastric and brain tumor. Similarly among different isozymes of carbonic anhydrase (CA), CA II is expressed in pancreatic, gastric carcinomas as well as in brain tumors. Therefore, novel potent inhibitors of both 15-LOX and CA II are required to explore the role of these enzymes further and to enable the drug discovery efforts. For this purpose, a series of benzyledinyl-hydrazinyl substituted thiazole derivatives were designed, synthesized and characterized by FTIR, 1H, &13C NMR spectroscopy. The derivatives were then evaluated for their potential to inhibit 15-LOX and bovine carbonic anhydrase II (bCA II). Most of these compounds showed excellent inhibitory potential for 15-LOX with an IC50 of 0.12 ± 0.002 to 0.69 ± 0.5 μM and showed moderate inhibition potency for bCA II with compound 5h (IC50 = 1.26 ± 0.24 μM) being the most active. The most potent compound 5a that emerged as a dual inhibitor of both enzymes, exhibiting 24 times greater selectivity for 15-LOX over bCA II. Compound 5a exhibited dual potent inhibitory activity against both 15-LOX and bCA II enzymes having IC50 values of 0.12 ± 0.002 and 2.93 ± 0.22 μM, respectively. Molecular docking studies of potent as well as dual inhibitors were also carried out to provide an insight into the binding site interactions. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/27836541/Substituted__E__2__2_benzylidenehydrazinyl__4_methylthiazole_5_carboxylates_as_dual_inhibitors_of_15_lipoxygenase_&_carbonic_anhydrase_II:_synthesis_biochemical_evaluation_and_docking_studies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(16)31883-6 DB - PRIME DP - Unbound Medicine ER -