Synthesis and Anti-bacterial Properties of Mono-carbonyl Analogues of Curcumin

Abstract

Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, Fig. 1], a compound isolated from Curcuma longa L., has been used for centuries as dietary pigment and spice. Curcumin has been found to possess a variety of traditional pharmaceutical applications on diseases, including external/internal wounds, liver diseases (particularly jaundice), blood purification, microbial effects and inflamed joints.1-4) Over a period of research, curcumin was reported to inhibit carcinogen-induced mutations and the formation of tumour in several experimental systems, 5-7) and exhibit anti-proliferation capability as a potent tool in cancer therapy. 8,9) Curcumin has also been reported to inhibit bacterial lipopolysaccharide-induced TNF-a overexpression and the transcription factor nuclear factor kappa B (NF-kB) activation which are involved in several pathogen-infected diseases. 2,10) Preclinical and clinic studies showed that, however, curcumin possesses several disadvantages in pharmacokinetics such as poor bioavailability, fast metabolism and requiring repetitive oral doses, 11,12) which limited its applications. However, curcumin is still an excellent lead compound for drug design and development on the basis of the explicit bioactivities, non-toxicity and easy synthesis. [13][14][15][16] Curcumin is stable at a pH below 6.5. The instability of curcumin at a pH above 6.5 is caused by the methylene group. 17)Omitting the methylene group and one carbonyl group, B. M. Markaverich, 18) M. Artico, 19) and H. I. El-Subbagh 20) synthesized series of mono-carbonyl curcumin analogues, 1,5-diaryl-1,4-pentadiene-3-ones, and evaluated their bioactivity. The result that the mono-carbonyl analogues exhibit more powerful inhibition in a variety of cancer cells than curcumin indicated that the central methylene group which had been considered the main active group of curcuminoids in antitumor property may be of decreasing importance.Therefore, in the present paper three series of mono-carbonyl curcumin analogues without the central methylene functional groups, 1,5-diaryl-1,4-pentadiene-3-ones (B), together with cyclopentanone (A) and cyclohexanone (C) analogues (Fig. 2), were prepared and their anti-bacterial properties in vitro were evaluated and compared using seven multidrug-resistant bacteria specially causing secondary infections in human being.21) These compounds were also designed to examine the role of different substitutes in the benzene ring and the influence of the space structure of the linking C-strain. It is hoped that continued research will lead to development of new lead compounds from curcumin as antibacterial agents and extrapolated agents for bacteria-infected diseases. Bioreactor and Pharmaceutical Development, Jilin Agricultural University; Changchun 130118, P. R. China. Received August 14, 2007; accepted November 7, 2007 The synthesis of three series of curcumin analogues with mono-carbonyl is described. Their in vitro antibacterial activities against seven Gram-positive and Gram-negative bacteria ...

A New Cyclooxygenase-2 Inhibitor, (1E,4E)-1,5-Bis(2-bromophenyl)penta-1,4-dien-3-one (GL63) Suppresses Cyclooxygenase-2 Gene Expression in Human Lung Epithelial Cancer Cells: Coupled mRNA Stabilization and Posttranscriptional Inhibition

“…Our preliminary studies indicated that some monocarbonyl analogues not only were able to enhance stability and antitumor activities in vitro but also have better pharmacokinetic profiles in vivo. 11,12,22,30) In this study, we demonstrated that a new analogue, GL63, is more potent than curcumin in inhibiting PMA-induced COX-2 mRNA and protein expression (Figs. 2, 3).…”

“…Cyclooxygenase-2 Inhibitor, (1E,4E) Synthesis of GL63 The general procedure used for the synthesis of GL63 is described below. 22) An aliquot of 7.5 mmol of acetone was added to a solution of 15 mmol of arylaldehyde in MeOH (10 ml). The solution was stirred at room temperature for 20 min, followed by dropwise addition of NaOCH 3 /CH 3 OH (1.5 ml; 7.5 mmol).…”

A novel mono-carbonyl analogue of curcumin induces apoptosis in ovarian carcinoma cells via endoplasmic reticulum stress and reactive oxygen species production

“…In previous studies, we designed and synthesized a series of mono-carbonyl analogues of curcumin with more stability and better pharmacokinetic profiles. We also demonstrated that some of the analogues exhibited better antitumor activity compared to curcumin (13)(14)(15)(16).…”

Synthesis and Cytotoxic Evaluation of Monocarbonyl Analogs of Curcumin as Potential Anti‐Tumor Agents

“…(2E,5E)−2,5‐bis(4‐hydroxy‐3‐methoxybenzylidene)cyclopentanone ( 4a ), (1E,4E)−1,5‐bis (4‐hydroxy‐3‐methoxyphenyl)penta‐1,4‐dien‐3‐one ( 4b ) and (2E,5E)−2,5‐bis(4‐hydroxy‐3‐methoxybenzylidene) cyclohexanone ( 4c ) were prepared as described in the literature. [Liang et al, 2008]. …”