Eliminating the Heart from the Curcumin Molecule: Monocarbonyl Curcumin Mimics (MACs)

• Type of Material: Article
• Authors: Dinesh Shetty, Emory University; Yong Joon Kim, Emory University; Hyunsuk Shim, Emory University; James P Snyder, Emory University
• Language: English
• Date: 2015-01-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2014 by the authors; licensee MDPI, Basel, Switzerland
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/molecules20010249
• Title of Journal or Parent Work: Molecules
• ISSN: 1420-3049
• Volume: 20
• Issue: 1
• Start Page: 249
• End Page: 292
• Grant/Funding Information: We are grateful to the NIH (R01CA165306) for support to make this work possible.
• Keywords: Chemistry; LUNG-CANCER CELLS; inflammation; POTENT IN-VIVO; Science & Technology; MONO-CARBONYL ANALOGS; ANTIINFLAMMATORY AGENTS; VITRO ANTICANCER ACTIVITY; NF-kappa B; NF-KAPPA-B; anti-angiogenesis; MACs; cancer; ENDOPLASMIC-RETICULUM STRESS; infectious disease; CRYSTAL-STRUCTURE; monocarbonyl analogs of curcumin; Chemistry, Organic; MYCOBACTERIUM-TUBERCULOSIS; TNF-alpha; INDUCED INFLAMMATORY RESPONSE; Physical Sciences
• Research Categories: Chemistry, Radiation; Chemistry, General

Abstract

Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin's Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ∼ 7.4. Researchers have sought to unlock curcumin's assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs). A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10-20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK) profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer's disease and malaria.