Cancer is a dreadful disease and, in most cases, leads to death even when it is being treated. Even though synthetic drugs are still in use for the treatment of cancer, the seriousness of the side effects of these drugs has boggled researcher’s mind to find more effective drugs which will help to overcome the side effects and have greater potency in trying to make the patient completely free of the disease. Recently, researchers turned their attention towards bio-components present in natural products. Curcumin, a polyphenol and the main constituent of a rhizome Curcuma longa, has geared significant interest due to its wide spectrum of therapeutics values, especially anticancer activity. Paper summarizes the chemistry and bio-metabolism of curcumin in the human body. Aim of this review article is to gather the dispersed efforts of researchers predominantly in improving the bioavailability of curcumin. In the present review, comprehensive literature on anticancer activity of Curcumin via combination therapy, structure modification, synthesis of analogues, novel delivery systems have been highlighted. Besides, the review paper explicated several challenges associated with Curcumin as an adjuvant chemotherapeutic agent and emphasizes more on clinical studies.
Background: Despite the development of numerous customized techniques for treating breast cancer, cancer patients' clinical results revealed adverse consequences in addition to chemotherapeutic drug resistance. Hence, finding therapeutic compounds with little or no side effects becomes essential in the fight against cancer. Resveratrol, a naturally occurring non-flavonoid polyphenol present in plants as a phytoalexin, is a promising therapeutic agent that has garnered the interest of several researchers due to its prodigious pharmacological and biological activities, but its unfavourable pharmacokinetic properties complicated its clinical studies. Along with several structural modifications, substitutions, etc., that have already been reported, this is the first time that a novel resveratrol analogue comprising an aromatic hetero moiety (ResD1) was synthesized using resveratrol isolated from grape (Vitis vinifera) peels as a precursor. Methods: ResD1 was synthesized by one-pot reaction using extracted and isolated resveratrol from grape peels. Structure confirmation of the isolated resveratrol and synthesized resveratrol derivative was elucidated by 1H-NMR, 13C-NMR, FTIR, and LC-MS. In silico molecular docking and ADMET study of ResD1 were carried out using AutoDock 4.2 and ADMETLab 2.0. ResD1 was evaluated for in vitro antioxidant, antimicrobial, anticancer, and CAXII gene expression as per the standard methods. Results: In silico molecular docking results revealed that ResD1 is capable of attaching to the ERα (estrogen receptor alpha) protein via hydrogen and hydrophobic bonds and has -7.12 kcal/mol as docking score. The novel derivative (IC50 = 42.8 µg/ml) exhibited better radical scavenging ability than ascorbic acid (control). The antimicrobial activities exemplify that it can induce microbial cell death for all the strains at higher concentrations. MTT assay results portrayed the potent antiproliferative activity against MCF-7 cell lines (IC50 = 155.2 µg/ml) and non-cytotoxicity for MDA-MB-231 cell lines. Moreover, the synthesized resveratrol derivative induced ROS (reactive oxygen species) levels in MCF-7 cells, indicating cytotoxicity. CAXII gene expression study showed that it downregulated the CAXII genes. Conclusion: This study serves as an example of how a newly proposed resveratrol analogue might be utilized as a viable pharmacophore for specifically targeting the ER alpha protein which will be beneficial in investigating a fresh batch of effective resveratrol mimics as prospective anticancer agents.
A novel series of piperazine analogs were synthesized comprising azole moieties with good yield. Structures of all four synthesized azole analogs were established by spectral characterization viz 1 H-nuclear magnetic resonance, liquid chromatography-mass spectrometry , and FT-IR. Synthesized derivatives were further assessed for their antimicrobial and antioxidant studies. Antimicrobial activity was conducted against Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans by well diffusion method. Antimicrobial activity reflects that synthesized piperazine derivatives containing imidazole moiety possess better antibacterial and antifungal activity than piperazine analogs comprising triazole moiety. Staphylococcus aureus exhibited strong resistance over all synthesized piperazine derivatives. Antioxidant activity of synthesized molecules were carried out by using 1, 1-diphenyl-2-picrylhydrazyl. In vitro antioxidant activity results revealed that IC50 values of synthesized piperazine analogs are comparative with control-gallic acid where piperazine derivatives with triazole unit ITZ-1 and ITZ-2 are exhibiting better antioxidant activities. Hence, synthesized novel molecules with better antimicrobial and antioxidant activities may be further used in the formulation of new antimicrobial and antioxidant drugs. Observed IC50, zone of inhibition values and drug resistance of S. aureus strain against all synthesized novel piperazine derivatives in the present investigation will be helpful to be used as a reference for auxiliary studies and further evaluation is worth to develop a new generation drug.
Amplified expression of mutations in proteins is an important hallmark of malignant cancer. In all RAS-mutant human cancers, pancreatic ductal adenocarcinoma (PDAC) is considered the most RAS-fanatic cancer, with a frequency of 100% KRAS (Kirsten rat sarcoma virus) mutation. In the present work, curcumin, a dietary phytochemical, was used to design a series of novel curcumin analogues aiming to regulate KRAS protein. The molecular docking study revealed the ligand efficacy and binding affinity of designed curcumin analogues against target proteins. Drug-like behaviour and ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction of identified molecules were done, and most of the pharmacokinetic parameters were found to be quite satisfactory and within an acceptable range. Three of the most potent drug candidates have been synthesized and characterized by FTIR, 1HNMR, and LC-MS spectral analysis. Results of the in vitro anti-proliferative activities of curcumin analogues showed persuasive anticancer activity against the PANC-1 cell lines. The present study will be helpful in exploring the new series of cogent curcumin analogues as anticancer agents.
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