Benzo[d]isothiazole 1,1-dioxide derivatives as dual functional inhibitors of 5-lipoxygenase and microsomal prostaglandin E(2) synthase-1

Erchang Shang; Yiran Wu; Pei Liu; Ying Liu; Wei Zhu; Xiaobing Deng; Chong He; Shan He; Cong Li; Luhua Lai

doi:10.1016/j.bmcl.2014.04.006

Benzo[d]isothiazole 1,1-dioxide derivatives as dual functional inhibitors of 5-lipoxygenase and microsomal prostaglandin E(2) synthase-1

Bioorg Med Chem Lett. 2014 Jun 15;24(12):2764-7. doi: 10.1016/j.bmcl.2014.04.006. Epub 2014 Apr 13.

Authors

Erchang Shang¹, Yiran Wu², Pei Liu¹, Ying Liu³, Wei Zhu¹, Xiaobing Deng⁴, Chong He¹, Shan He¹, Cong Li¹, Luhua Lai⁵

Affiliations

¹ BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
² BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Center for Quantitative Biology, Peking University, Beijing 100871, China.
³ BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Center for Quantitative Biology, Peking University, Beijing 100871, China. Electronic address: [email protected].
⁴ Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
⁵ BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Center for Quantitative Biology, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.

PMID: 24794107
DOI: 10.1016/j.bmcl.2014.04.006

Abstract

A series of 6-nitro-3-(m-tolylamino) benzo[d]isothiazole 1,1-dioxide analogues were synthesized and evaluated for their inhibition activity against 5-lipoxygenase (5-LOX) and microsomal prostaglandin E2 synthase (mPGES-1). These compounds can inhibit both enzymes with IC50 values ranging from 0.15 to 23.6μM. One of the most potential compounds, 3g, inhibits 5-LOX and mPGES-1 with IC50 values of 0.6μM, 2.1μM, respectively.

Keywords: 5-Lipoxygenase; Benzo[d]isothiazole 1,1-dioxide; Dual functional inhibitor; Microsomal prostaglandin E(2) synthase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzothiazoles / chemical synthesis*
Benzothiazoles / chemistry
Benzothiazoles / pharmacology
Binding Sites
Enzyme Activation / drug effects
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Inhibitory Concentration 50
Intramolecular Oxidoreductases / antagonists & inhibitors*
Lipoxygenase Inhibitors*
Microsomes / drug effects*
Microsomes / enzymology*
Microsomes / metabolism
Models, Molecular
Prostaglandin-E Synthases

Substances

Benzothiazoles
Enzyme Inhibitors
Lipoxygenase Inhibitors
Intramolecular Oxidoreductases
Prostaglandin-E Synthases