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Review

Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer

by
Amarjyoti Das Mahapatra
1,
Rinku Choubey
1 and
Bhaskar Datta
1,2,*
1
Department of Chemistry, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar 382355, India
2
Department of Biological Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar 382355, India
*
Author to whom correspondence should be addressed.
Molecules 2020, 25(23), 5488; https://doi.org/10.3390/molecules25235488
Submission received: 28 October 2020 / Revised: 13 November 2020 / Accepted: 19 November 2020 / Published: 24 November 2020
(This article belongs to the Section Medicinal Chemistry)

Abstract

The enzyme soluble epoxide hydrolase (sEH) plays a central role in metabolism of bioactive lipid signaling molecules. The substrate-specific hydrolase activity of sEH converts epoxyeicosatrienoic acids (EETs) to less bioactive dihydroxyeicosatrienoic acids. EETs exhibit anti-inflammatory, analgesic, antihypertensive, cardio-protective and organ-protective properties. Accordingly, sEH inhibition is a promising therapeutic strategy for addressing a variety of diseases. In this review, we describe small molecule architectures that have been commonly deployed as sEH inhibitors with respect to angiogenesis, inflammation and cancer. We juxtapose commonly used synthetic scaffolds and natural products within the paradigm of a multitarget approach for addressing inflammation and inflammation induced carcinogenesis. Structural insights from the inhibitor complexes and novel strategies for development of sEH-based multitarget inhibitors are also presented. While sEH inhibition is likely to suppress inflammation-induced carcinogenesis, it can also lead to enhanced angiogenesis via increased EET concentrations. In this regard, sEH inhibitors in combination chemotherapy are described. Urea and amide-based architectures feature prominently across multitarget inhibition and combination chemotherapy applications of sEH inhibitors.
Keywords: soluble epoxide hydrolase (sEH) inhibitors; urea derivatives; inflammation; combination chemotherapy; multitarget therapy soluble epoxide hydrolase (sEH) inhibitors; urea derivatives; inflammation; combination chemotherapy; multitarget therapy

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MDPI and ACS Style

Das Mahapatra, A.; Choubey, R.; Datta, B. Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer. Molecules 2020, 25, 5488. https://doi.org/10.3390/molecules25235488

AMA Style

Das Mahapatra A, Choubey R, Datta B. Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer. Molecules. 2020; 25(23):5488. https://doi.org/10.3390/molecules25235488

Chicago/Turabian Style

Das Mahapatra, Amarjyoti, Rinku Choubey, and Bhaskar Datta. 2020. "Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer" Molecules 25, no. 23: 5488. https://doi.org/10.3390/molecules25235488

APA Style

Das Mahapatra, A., Choubey, R., & Datta, B. (2020). Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer. Molecules, 25(23), 5488. https://doi.org/10.3390/molecules25235488

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