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Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3-oxazine derivatives.
Drug Dev Res. 2018 11; 79(7):352-361.DD

Abstract

Hit, Lead & Candidate Discovery A series of 1-(6-methyl-2-substituted phenyl-4-thioxo-4H-1,3-oxazin-5-yl)ethanones (3a-n) were synthesized by the reaction of benzoyl isothiocyanates with active methylene compound acetylacetone in the presence of triethyl amine in a one-pot process. The structures of the products were elucidated by elemental analyses, FT-IR, 1 H NMR, 13 C NMR, and mass spectroscopy. These new 1,3-oxazine derivatives were evaluated for their inhibitory activity against carbonic anhydrase II. Results for in vitro assay revealed that compound 3b having 4-methoxy phenyl moiety was the most potent inhibitor with IC50 value of 0.144 ± 0.008 μM. It exhibited higher enzyme inhibitory activity as compared to the standard acetazolamide (IC50 = 0.997 ± 0.061 μM). The compounds 3c, 3h, and 3n also displayed superior inhibitory activities compared to the rest of the synthesized oxazine derivatives. The radical scavenging activity of oxazine derivatives was also performed and it was found that compounds showed moderate antioxidant activity. Lipinski rule confirmed the therapeutic potential of the synthesized compounds. Molecular docking studies were also performed to further understand the binding affinity of these compounds with PDBID 1V9E which confirmed that the synthesized derivatives bind in the active binding site of the target protein. Based upon our results, it is proposed that compound 3b may serve as a lead structure to design more potent carbonic anhydrase inhibitors.

Authors+Show Affiliations

Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.Department of Chemistry, Allama Iqbal Open University, Islamabad, Pakistan.Department of Physiology, University of Sindh, Jamshoro, Pakistan.Department of Biology, College of Natural Sciences, Kongju National University, Gongju, Republic of Korea.School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30302774

Citation

Qamar, Rabia, et al. "Synthesis, Carbonic Anhydrase Inhibitory Activity and Antioxidant Activity of some 1,3-oxazine Derivatives." Drug Development Research, vol. 79, no. 7, 2018, pp. 352-361.
Qamar R, Saeed A, Saeed M, et al. Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3-oxazine derivatives. Drug Dev Res. 2018;79(7):352-361.
Qamar, R., Saeed, A., Saeed, M., Ashraf, Z., Abbas, Q., Hassan, M., & Albericio, F. (2018). Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3-oxazine derivatives. Drug Development Research, 79(7), 352-361. https://doi.org/10.1002/ddr.21464
Qamar R, et al. Synthesis, Carbonic Anhydrase Inhibitory Activity and Antioxidant Activity of some 1,3-oxazine Derivatives. Drug Dev Res. 2018;79(7):352-361. PubMed PMID: 30302774.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3-oxazine derivatives. AU - Qamar,Rabia, AU - Saeed,Aamer, AU - Saeed,Maria, AU - Ashraf,Zaman, AU - Abbas,Qamar, AU - Hassan,Mubashir, AU - Albericio,Fernando, Y1 - 2018/10/10/ PY - 2018/04/20/received PY - 2018/08/10/revised PY - 2018/08/14/accepted PY - 2018/10/12/pubmed PY - 2019/6/6/medline PY - 2018/10/11/entrez KW - 1,3-oxazine KW - acyl isothiocyanates KW - antioxidant activity KW - carbonic anhydrase inhibition KW - molecular docking SP - 352 EP - 361 JF - Drug development research JO - Drug Dev. Res. VL - 79 IS - 7 N2 - Hit, Lead & Candidate Discovery A series of 1-(6-methyl-2-substituted phenyl-4-thioxo-4H-1,3-oxazin-5-yl)ethanones (3a-n) were synthesized by the reaction of benzoyl isothiocyanates with active methylene compound acetylacetone in the presence of triethyl amine in a one-pot process. The structures of the products were elucidated by elemental analyses, FT-IR, 1 H NMR, 13 C NMR, and mass spectroscopy. These new 1,3-oxazine derivatives were evaluated for their inhibitory activity against carbonic anhydrase II. Results for in vitro assay revealed that compound 3b having 4-methoxy phenyl moiety was the most potent inhibitor with IC50 value of 0.144 ± 0.008 μM. It exhibited higher enzyme inhibitory activity as compared to the standard acetazolamide (IC50 = 0.997 ± 0.061 μM). The compounds 3c, 3h, and 3n also displayed superior inhibitory activities compared to the rest of the synthesized oxazine derivatives. The radical scavenging activity of oxazine derivatives was also performed and it was found that compounds showed moderate antioxidant activity. Lipinski rule confirmed the therapeutic potential of the synthesized compounds. Molecular docking studies were also performed to further understand the binding affinity of these compounds with PDBID 1V9E which confirmed that the synthesized derivatives bind in the active binding site of the target protein. Based upon our results, it is proposed that compound 3b may serve as a lead structure to design more potent carbonic anhydrase inhibitors. SN - 1098-2299 UR - https://www.unboundmedicine.com/medline/citation/30302774/Synthesis_carbonic_anhydrase_inhibitory_activity_and_antioxidant_activity_of_some_13_oxazine_derivatives_ L2 - https://doi.org/10.1002/ddr.21464 DB - PRIME DP - Unbound Medicine ER -