Curcumin: Synthesis optimization andin silicointeraction with cyclin dependent kinase

Abstract

Curcumin: Synthesis optimization and in silico interaction with cyclin dependent kinaseCurcumin is a natural product with enormous biological potential. In this study, curcumin synthesis was revisited using different reaction solvents, a catalyst (n-butylamine) and a water scavenger [(n-BuO) 3 B], to develop the optimal procedure for its rapid acquisition. During synthesis, solvent choice was found to be an important parameter for better curcumin yield and high purity. In a typical reaction, acetyl acetone was treated with boron trioxide, followed by condensation with vanillin in the presence of tri-n-butyl borate as water scavenger and n-butylamine as catalyst at 80 °C in ethyl acetate to afford curcumin. Moreover, curcumin was also extracted from turmeric powder and spectroscopic properties such as IR, MS, 1 H NMR and 13 C NMR with synthetic curcumin were established to identify any impurity. The purity of synthetic and extracted curcumin was also checked by TLC and HPLC-DAD. To computationally assess its therapeutic potential against cyclin dependent kinases (CDKs), curcumin was docked in different isoforms of CDKs. It was observed that it did not dock at the active sites of CDK2 and CDK6. However, it could enter into weak interactions with CDK4 protein.Keywords: curcumin synthesis, CDKs, molecular docking Curcumin (C) is a phenolic compound that is considered to be a bioactive component of turmeric. Since ancient times it has been an integral part of ancient herbal medicine. Nowadays, it is widely used in medicine and in diet supplements. Structurally, curcumin exists in keto and enol tautomeric forms due to intra-molecular hydrogen bonding between keto carbonyl oxygen and an enolic hydrogen atom (1). Possible therapeutic potential of curcumin was revealed in the last decades. Different studies have explained its efficacy against various types of cancers such as chemo resistant colon cancer cells, esophageal cancers, thyroid carcinomas, skin cancer (2) and as a potent anti-inflammatory agent (3). Curcumin regulates various growth factors, protein kinases, inflammatory cytokines and transcription factors to suppress the metastases and proliferation of human tumors (4). Other than anticancer and antitumor activities, it has also shown its effects against a variety of diseases such as respiratory tract infection, hepatic steatosis, skin photoageing, Parkinson's disease, pathogenesis of obesity, diabetes, HIV-associated diarrhea and Alzheimer's disease, through inhibition of amyloid beta oligomer formation (5-8). The structure-activity relationship studies of curcumin molecule against different biological targets have indicated that the presence of two phenyl rings with a C-7 linker with ketoenol function (C=O groups as hydrogen acceptors and C-4 as a hydrogen donor) are most important for its biological activities. However, unsaturation in the linker (conformational flexibility) is important for its antitumor/anticancer activity but not for redox regulatory or apoptotic activities (9). Synthetic methodology to...

Curcuminoids versus Pyrazole‐Modified Analogues: Synthesis and Cytotoxicity against HepG2 Cancer Cell Line

“…The synthetic yields of aldol condensation reactions between benzaldehyde analogues and pentane-2,4-dione to generate curcuminoids (1-10) are dependent on several factors including solvent, catalyst, reaction time, complexing agent, water scavenger and temperature [5,6,9,21,22,31] (see the Supporting Information for the synthetic procedure). The ratio of aldehyde and pentane-2,4-dione (2 : 1) would minimize side reactions due to the consumption of reactants.…”

Principal Component Analysis Based Solvent Map for Optimisation of Rate and Yield of Curcumin Synthesis

“…The solvent screening were carried out ussually by an experimental process of trial-and-error. This work required much time due to many experiments, and therefore has missed some actually optimum solvents among possible solvents [9,10].…”

The Effect of Curcumin on the Differentiation of Mesenchymal Stem Cells into Mesodermal Lineage

“…Curcumin not only increases the p27 accumulation but also improves the half-life of the protein. An increased p27 amount and stability suppresses cell division and therefore suppresses the early stage of adipogenic differentiation [35,37,38]. Cdk2 phosphorylates both C/EBPβ, which is essential for the transcriptional activation of PPARγ, and C/EBPα, during the early stage of adipocyte differentiation [39].…”