Novel cinnamic acid derivatives as antioxidant and anticancer agents: design, synthesis and modeling studies (original) (raw)
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Cinnamic acids have been identified as interesting compounds with antioxidant, anti-inflammatory and cytotoxic properties. In the present study, simple cinnamic acids were synthesized by Knoevenagel condensation reactions and evaluated for the above biological activities. Compound 4ii proved to be the most potent LOX inhibitor. Phenyl-substituted acids showed better inhibitory activity against soybean LOX, and it must be noted that compounds 4i and 3i with higher lipophilicity values resulted less active than compounds 2i and 1i. The compounds have shown very good activity in different antioxidant assays. The antitumor properties of these derivatives have been assessed by their 1/IC 50 inhibitory values in the proliferation of HT-29, A-549, OAW-42, MDA-MB-231, HeLa and MRC-5 normal cell lines. The compounds presented low antitumor activity considering the IC 50 values attained for the cell lines, with the exception of compound 4ii. Molecular docking studies were carried out on cinnamic acid derivative 4ii and were found to be in accordance with our experimental biological results.
Multifunctional Cinnamic Acid Derivatives
Molecules, 2017
Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino) ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX) inhibition (IC 50 = 6 µM) and antiproteolytic activity (IC 50 = 0.425 µM). The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC 50 = 0.315 µM) and good LOX inhibitory activity (IC 50 = 66 µM). Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.
Evaluation of the Antitumor and Chemopreventive Potential of Cinnamoyl-Based Compounds
2013
2013 vii 2.2.17 Enzyme-linked immunosorbent assay (ELISA) 76 2.2.18 Statistical analysis 78 CHAPTER Cell cycle disruption and induction of apoptosis by cinnamaldehydes 79 3.1 Introduction 80 3.2 Results 81 3.2.1 Growth inhibition and cytotoxicity of cinnamaldehydes against HCT 116 and MCF-7 cell lines 81 3.2.2 Induction of cell cycle arrest in G 2 phase by cinnamaldehydes 85 3.2.3 Dysregulation of cell cycle proteins by cinnamaldehydes 90 3.3 Discussion 98 CHAPTER 4 Induction of tubulin aggregation by cinnamaldehydes 4.1 Introduction 4.2 Results 4.2.1 Investigation of the possible interaction between cinnamaldehydes and tubulin 4.2.2 Induction of tubulin aggregation by cinnamaldehydes 4.3 Discussion CHAPTER 5 Investigation of the cancer-preventive potential of cinnamaldehydes viii 5.2.4 Investigation of the possible effect of BCA on Nrf2-p21 5.3 Discussion CHAPTER 6 Evaluation of the cinnamoyl-based 'supercinnamaldehydes' for their cancer-preventive potential CHAPTER 1
Synthesis and characterization of new derivatives of cinnamic acid
Aseries of new derivatives 1-11 of cinnamic acid have been synthesized by a facile procedure for esterification based on using of DCC as a coupling agent, DMAP and solvent system methylene chloride. The structures of all the newly synthesized derivatives 1-11 of cinnamic acid were assigned as 3-methyl-2-butenyl (E)-3-(3,4,5-trihydroxyphenyl)-2-propenoate (1), (2E)-3,7-dimethyl-2,6-octadienyl (E)-3-(3,4,5-trihydroxyphenyl)-2-propenoate (2), (2Z)-3,7-dimethyl-2,6-octadienyl (E)-3-(3,4,5-trihydroxyphenyl)-2-propenoate (3), (2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrienyl (E)-3-(3,4,5- trihydroxyphenyl)-2-propenoate (4), (2E)-3,7-dimethyl-2,6-octadienyl (E)-3- (4-hydroxy-3-methoxyphenyl)-2-propenoate (5), (2Z)-3,7-dimethyl-2,6- octadienyl (E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate (6), (2E,6E)- 3,7,11-trimethyl-2,6,10-dodecatrienyl (E)-3-(4-hydroxy-3-methoxyphenyl)-2- propenoate (7), 3-methyl-2-butenyl (E)-3-(4-hydroxy-3,5-dimethoxyphenyl)- 2-propenoate (8), (2E)-3,7-dimethyl-2,6-octadienyl (E)-3-(4-hydroxy-3,5- dimethoxyphenyl)-2-propenoate (9), (2Z)-3,7-dimethyl-2,6-octadienyl (E)-3- (4-hydroxy-3,5-dimethoxyphenyl)-2-propenoate (10) and (2E,6E)-3,7,11- trimethyl-2,6,10-dodecatrienyl (E)-3-(4-hydroxy-3,5-dimethoxyphenyl)-2- propenoate (11) by extensive NMR studies
European journal of …, 2004
A series of esters (I a-k ), substituted derivatives (II a-d ) and amides (III a-q ) of cinnamic acid were synthesized and evaluated as antibacterial and antifungal agents. All the derivatives belonging to the series I, II and III showed antimicrobial activity comparable to the standard. Compounds I f and II c proved to be the most effective compounds. Quantitative structure-activity relationship (QSAR) investigation with multiple linear regression analysis was applied to find a correlation between different calculated physicochemical parameters of the compounds and biological activity. The quantitative models relating the structural features of cinnamic acid derivatives I a-k , II a-d and III a-q and their antimicrobial activity showed that Gram negative Escherichia coli and Candida albicans (fungus) were the most sensitive microorganisms.
2015
Several cinnamic acid esters were obtained via Fischer esterification of cinnamic acids derivatives with aliphatic alcohols. Cinnamic acids derivatives were synthesized via Knoevenagel reaction between substituted benzaldehydes and malonic acid in aqueous medium assisted by microwave heating. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. panamensis amastigotes and cytotoxic activity against U-937 cells. The compounds 6, 10-12 and 18, were active against Leishmania parasite but toxic for mammalian cells. They are potential candidates for antileishmanial drug development.
Innovare Journal of Life Science, 2023
Objective: The pathology of every disease passes through the inflammation stage; hence, the design and optimization of potential lead compounds as anti-inflammatory agents is still a significant part of medicinal chemistry globally. Methods: In this study, we designed, synthesized, and characterized some cinnamic acid derivatives and performed molecular docking of the derivatives on the human cyclooxygenase-1 (COX-1) enzyme. Results: The elemental analysis showed the presence of different functional groups. Molecular docking was performed on the active sites of COX-1 (PDB ID: 6Y3C). The derivatives as well as the standard compound, were observed to interact mainly with the arginine residue of the target protein. The dioxomethylene substituted derivative showed the highest binding affinity, compared with other derivatives, including the standard drug (−6.8 kcal/mol). Conclusion: The binding affinity observed in the cinnamic derivatives, and biological activities correlations revealed that compounds with the dioxomethylene group would be good anti-inflammatory lead molecules, as they demonstrated high affinity to the target protein and biological activities. Thus, these compounds can serve as potential lead compounds for the design, and development of effective anti-inflammatory agents, targeted to inhibit the human COX-1 enzyme involved in biological inflammatory mechanisms.
Structure−Antifungal Activity Relationship of Cinnamic Acid Derivatives
Journal of Agricultural and Food Chemistry, 2007
A structure-antifungal activity relationship (SAR) study of 22 related cinnamic acid derivatives was carried out. Attention was focused on the antifungal activities exhibited against Aspergillus flavus, Aspergillus terreus, and Aspergillus niger. (E)-3-(4-Methoxy-3-(3-methylbut-2-enyl)phenyl)acrylic acid (16) exhibited antifungal activity against A. niger, comparable to that of miconazole and a significant antifungal effect against A. flavus and A. terreus as well. A structure-activity relationship (SAR) study of related cinnamic acid derivatives has allowed a model to be proposed for the recognition of the minimal structural requirements for the antifungal effect in this series.