Curcumin and Its Carbocyclic Analogs: Structure-Activity in Relation to Antioxidant and Selected Biological Properties

Abstract

Curcumin is the major phenolic compound present in turmeric (Curcuma longa L.). Curcumin and 15 novel analogs were investigated for their antioxidant and selected biological activities. Strong relationships between the structure and evaluated activity revealed that the compounds with specific functional groups and carbon skeleton had specific biological profiles. Among the compounds tested, the derivatives (E)-2-(3,4-dimethoxybenzylidene)-5-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclopentanone (3e), and (E)-2-(4-hydroxy-3-methoxybenzylidene)-5-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)-cyclopentanone (3d) and the parent compound curcumin exhibited the strongest free radical scavenging and antioxidant capacity. Concerning the other biological activities studied the compound (E)-2-(4-hydroxy-3-methoxybenzylidene)-5-((E)-3-(4-hydroxy-3-methoxy-phenyl)-acryloyl)cyclopentanone (3d) was the most potent angiotensin converting enzyme (ACE) inhibitor, while the derivatives (E)-2-(4-hydroxybenzylidene)-6-((E)-3-(4-hydroxyphenyl)acryloyl)cyclohexanone (2b), (E)-2-(3,4-dimethoxybenzylidene)-6-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclohexanone (2e) and (E)-2-(3,4-dimethoxybenzylidene)-5-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclopentanone (3e) exhibited strong tyrosinase inhibition. Moreover, (E)-2-(3,4-dimethoxybenzylidene)-6-((E)-3-(3,4-dimethoxyphenyl)-acryloyl)cyclohexanone (2e) was also found to be the strongest human HIV-1 protease inhibitor in vitro among the tested compounds. Cytotoxicity studies using normal human lung cells revealed that the novel curcumin as well as its carbocyclic analogs are not toxic.

Effect of Curcumin Against Oxidation of Biomolecules by Hydroxyl Radicals

“…The results showed the total anti-oxidant capacity of plasma exposed to hydroxyl radical increased when treated with curcumin in 3 rd , 4 th and 5 th groups [Table/ Fig-1,6]. This is in accordance with the studies of Weber WM et al, [47] and Bhullar KS et al, [48], who also estimated the total anti oxidant capacity of curcumin and its analogs.…”

Curcumin-inspired cytotoxic 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones: A novel group of topoisomerase II alpha inhibitors

“…Among our previous research, we have prepared and studied curcumin analogs where the diarylheptanoid skeleton of curcumin was retained (Series 1- Fig. 1) [15][16][17][18]. These studies involved evaluation of anticancer, antioxidant, antihypertensive, and/or anti-HIV properties of these compounds.…”

“…Continuous efforts in our lab are focused on analogs of curcumin in attempts to develop molecules with superior pharmacodynamic and pharmacokinetic profile than those of curcumin [15][16][17][18][19][20][21][22][23][24][25][26][27]. Among our previous research, we have prepared and studied curcumin analogs where the diarylheptanoid skeleton of curcumin was retained (Series 1- Fig.…”

Biological and therapeutic activities, and anticancer properties of curcumin

“…In Ayurvedic medicine, turmeric has been used for centuries for its medicinal properties (7) and has been administered through various routes, including topically, orally and by inhalation. It is well known that the curcumin exerts certain antioxidant, analgesic, anti-inflammatory and antimalarial properties (7)(8)(9)(10)(11)(12)(13)(14)(15).…”