Eliminating the heart from the curcumin molecule: Monocarbonyl curcumin mimics (MACs)
TL;DR: 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.
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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.
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Citations
Monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and resistant strains of Mycobacterium tuberculosis
Patrick R. Baldwin,Analise Z. Reeves,Kimberly R. Powell,Ruth J. Napier,Alyson Swimm,Aiming Sun,Kyle E. Giesler,Bettina Bommarius,Thomas M. Shinnick,James P. Snyder,Dennis C. Liotta,Daniel Kalman +11 more
TL;DR: Data provide a structural basis for the development of analogs of curcumin with pronounced anti-mycobacterial activity and provide a roadmap to develop additional structural analogs that exhibit more favorable interactions with other anti-TB drugs.
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Synthesis and Cytotoxicity Evaluation of Novel Asymmetrical Mono-Carbonyl Analogs of Curcumin (AMACs) against Vero, HeLa, and MCF7 Cell Lines.
TL;DR: Among the synthesized compounds, compound 1b was the most cytotoxic and selective against MCF7 cell lines and could be considered for further development to obtain the more active and selective chemotherapeutic agents against breast cancer.
Facile preparation, characterization, SC-XRD and DFT/DTDFT study of diversely functionalized unsymmetrical bis-aryl-α, β-unsaturated ketone derivatives
Muhammad Khalid,Akbar Ali,Muhammad Adeel,Zia Ud Din,Muhammad Tahir,Edson Rodrigues-Filho,Javed Iqbal,Muhammad Usman Khan +7 more
TL;DR: In this article, the synthesis of diversely functionalized unsymmetrical mono-carbonyl curcuminoids (MMMD, CMMD, and BMMD) is discussed.
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Antiparasitic activity of synthetic curcumin monocarbonyl analogues against Trichomonas vaginalis.
Caroline Carapina Da Silva,Bruna Silveira Pacheco,Raquel Nascimento Das Neves,Mirna Samara Dié Alves,Ângela Sena-Lopes,Sidnei Moura,Sibele Borsuk,Claudio M. P. Pereira +7 more
TL;DR: It is suggested that these analogues possess chemical features of interest to be further explored as alternatives for the treatment of trichomoniasis, demonstrating that the designed synthetic molecules not only have better chemical stability, but also higher anti-T.
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Chemoprevention of Leishmaniasis: In-vitro antiparasitic activity of dibenzalacetone, a synthetic curcumin analog leads to apoptotic cell death in Leishmania donovani
TL;DR: The present study reports the leishmanicidal activity of trans-dibenzalacetone (DBA), a synthetic monoketone analog of curcumin, against Leishmania donovani parasites and identifies an analog ofCurcumin for potential applications against leish maniasis, based on its strong antiparasitic activity and low toxicity.
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