Synthesis, applications and Structure-Activity Relationship (SAR) of cinnamic acid derivatives: a review

Authors

DOI:

https://doi.org/10.33448/rsd-v10i1.11691

Keywords:

Phytochemicals; Pharmacological; Pharmaceutical; Chemistry; Chemical Synthesis Techniques; Biosynthesis.

Abstract

The article aims to analyze the progress of the evolution of cinnamic acid derivatives through a bibliographic review, describing the main synthetic routes in obtaining this class, as well as remarkable biological applications and application of the structure-activity relationship (SAR) as a strategy for design pharmacologically active molecules. The methodology used consists of reading and analyzing articles, whose approach is descriptive, with data being collected regarding the therapeutic potential of derivatives of cinnamic acid and its relationship with structural scaffolding, as well as the most widely used synthetic approaches. As a result, it was observed that cinnamic acid and its derivatives from natural sources can be synthesized in appreciable quantities with varied synthetic routes, as well as being candidates for therapeutic agents, since they have several therapeutic applications against diabetes, infectious and degenerative diseases, among others, in addition to presenting activity such as pest control, which has attracted the attention of academic and industrial researchers. These compounds are highly versatile since their activity is intrinsically associated with the mode of interaction between the structure and its molecular target. However, in nature they are obtained in small quantities, therefore, the development of new approaches of synthetic methodologies to obtain such compounds in substantial quantities and linked to medicinal chemistry can contribute to the development of very effective bioactive molecules in comparison with their precursors.

References

Adisakwattana, S. (2017). Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications. Nutrients, 9 (163), 1−27.

Augustine, J. K., Boodappa, C., Venkatachaliah, S., & Mariappan, A. (2014). TiCl4-mediated olefination of aldehydes with acetic acid and alkyl acetates: a stereoselective approach to (E) α,β-unsaturated carboxylic acids and esters. Tetrahedron Letters, 55(24), 3503−3506.

Bai, Y., He, X., Bai, Y., Sun, Y., Zhao, Z., Chen, X., Li, B., Xie, J., Li, Y., Jia, P., Meng, X., Zhao, Y.,; Ding, Y., Xiao, C., Wang, S., Yu, J., Liao, S., Zhang, Y., Zhu, Z., Zhang, Q., Zhao, Y., Qin, F., Zhang, Y., Wei, X., Zeng, M., Liang, J., Cuan, Y., Shan, G., Fan, T. P., Wu, B., & Zheng, X. (2019). Polygala tenuifolia-Acori tatarinowii herbal pair as an inspiration for substituted cinnamic alfa-asaronol esters: Design, synthesis, anticonvulsant activity, and inhibition of lactate dehydrogenase study. European Journal of Medicinal Chemistry, 183, 111650.

Belsito, D., Bickers, D., Bruze, M., Calow, P., Greim, H., Hanifin, J. M., Rogers, A. E., Saurat, J. H., Sipes, I. G., & Tagami, H. (2007). A toxicologic and dermatologic assessment of related esters and alcohols of cinnamic acid and cinnamyl alcohol when used as fragrance ingredients Food and Chemical Toxicology. 45, S1−S23.

Bisogno, F., Mascoti, L., Sanchez, C., Garibotto, F., Giannini, F., Kurina-Sanz, M., & Enriz, R. (2007). Structure-antifungal activity relationship of cinnamic acid derivatives. Journal of Agricultural and Food Chemistry, 56(26), 10635 –10640.

Buxton, T., Takahashi, S., Doh, A. M. D., Ansah, J. B., Owusu, E. O., & Kim, C. S. (2019). Insecticidal activities of cinnamic acid esters isolated from Ocimum gratissimum L. and Vitellaria paradoxa Gaertn leaves against Tribolium castaneum Hebst (Coleoptera: Tenebrionidae). Pest Management Science, 76, 257 - 267.

Chen, D., Zhang, B., Liu, X., Li, X., Yang, X., & Zhou, L. (2018). Bioactivity and structure activity relationship of cinnamic acid derivatives and its heteroaromatic ring analogues as potential high-efficient acaricides against Psoroptes cuniculi. Bioorganic & Medicinal Chemistry Letters, 28 (6), 1149−1153.

Chiriac, C., Tanasa, F., & Onciu, M. (2005). A novel approach in cinnamic acid synthesis: direct synthesis of cinnamic acids from aromatic aldehydes and aliphatic carboxylic acids in the presence of boron tribromide. Molecules, 10(2), 481−487.

Cui, Y., Hu, Y. H., Yu, F., Zheng, J., Chen, L. S., Chen, Q. X., & Wang, Q. (2016). Inhibition kinetics and molecular simulation of p-substitutedcinnamic acid derivatives on tyrosinase International Journal of Biological Macromolecules, 11, 1289−1297.

De, P., Baltas, M., & Bedos-Belval, F. (2011). Cinnamic acid derivatives as anticancer agents-a review. Current Medicinal Chemistry, 18 (11), 1672−1703.

Doria, O. F. Maturana, R. A., RetamaL, A. B., Quintana, L. M., & Guzmán, L. (2019). N-alkylimidazolium salts functionalized with p-coumaric and cinnamic acid: a study of their antimicrobial and antibiofilm effects. Molecules, 24(19), 3484.

Fathi, E. Majdi, M., Dastan, D., & Marouf, A. (2019). The spatio-temporal expression of some genes involved in the biosynthetic pathways of terpenes/phenylpropanoids in yarrow (Achillea millefolium). Plant Physiology and Biochemistry, 142, 43−52.

Georgiev, L., Chochkova, M., Ivanova, G., Najdenski, H., Ninova, M., & Milkova, T. (2012). Radical scavenging and antimicrobial activities of cinnamoyl amides of biogenic monoamines. Riv. Ital. Sost. Grasse, 89(2), 91–102.

Ghafary, S., Ghobadian, R., Mahdavi, M., Nadri, H., Moradi, A., Akbarzadeh, T., Najafi, Z., Sharifzadeh, M., Edraki, N., Moghadam, F. H., & Amini, M. (2020). Design, synthesis, and evaluation of novel cinnamic acid-tryptamine hybrid for inhibition of acetylcholinesterase and butyrylcholinesterase. DARU Journal of Pharmaceutical Sciences, 28, 346-9

Ghasemzadeh, A., & Ghasemzadeh, N. (2011). Flavonoids and phenolic acids: role and biochemical activity in plants and human. Journal of Medicinal Plants Research, 5(31), 6697−6703.

Ghosh, S., Chisti, Y., & Banerjee, U. C. (2012). Production of shikimic acid. Biotechnology Advances, 30(6), 1425−1431.

Gunia-krzyżak, A., Słoczyńska, K., Popiół, J., Koczurkiewicz, P., Marona, H., & Pękala. (2018). Cinnamic acid derivatives in cosmetics – current use and future prospects running head: cinnamic acid derivatives in cosmetics. International Journal of Cosmetic Science, 40 (4), 356−366.

Guzman, J. D. (2014). Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity. Molecules, 19 (12), 19292−19349.

Hatsuda, M., Kuroda, T., & Seki, M. (2003). An Improved Synthesis of (E )-Cinnamic Acid Derivatives via the Claisen–Schmidt Condensation Synthetic Communications, 33(3), 427−434.

He, Y., & Cai, C. (2011). Polymer-supported macrocyclic schiff base palladium complex as an eficiente catalyst for the Heck reaction. Applied Organometallic Chemistry, 25, 799−803.

Hu, Y., Liu, X., Jia, Y., Guo, Y., Wang, Q., & Chen, Q. (2013). Inhibitory kinetics of chlorocinnamic acids on mushroom tyrosinase. Journal of Bioscience and Bioengineering, 117 (2), 142−146.

Imai, M., Yokoe, H., Tsubuki, M., &Takahashi, N. (2019). Growth inhibition of human breast and prostate cancer cells by cinnamic acid derivatives and their mechanism of action. Biological and Pharmaceutical Bulletin, 42(7), 1134−1139.

Jitareanu, A., Balan-porcarasu, M., & Tataringa, G. (2013). Cinnamic acid derivatives and 4-aminoantipyrine amides – synthesis and evaluation of biological properties. Research Journal of Chemical Sciences, 3 (3), 9−13.

Kooti, W., Servatyari, K., Behzadifar, M., Asadi-Samani, M., Sadeghi, F., Nouri, B., & Marzouni, H. Z. (2017). Effective medicinal plant in câncer treatment, part 2: review study. Journal of evidence-Based Complementary & Alternative Medicine, 22(4), 982 – 995.

Korosˇec, B., Sova, M., Turk, S., Krasˇevec, N., Novak, M., Lah, L., Stojan, J., Podobnik, B., Berne, S., Zupanec, N., Bunc, M., Gobec, S., & Kome, R. (2013). Antifungal activity of cinnamic acid derivatives involves inhibition of benzoate 4-hidroxylase (CYP53). Journal of Applied Microbiology, 116, 955−966.

Kozlov M., Konduktorov, K. A., Malikova, A., Kamarova, K. A., Shcherbakova, A. S., Solyev, P. N., & Kochetkov, S. N. (2019). Structural isomers of cinnamic hydroxamic acids block HCV replication via different mechanisms. European Journal of Medicinal Chemistry, 183, 111723.

Kumar, S. S., Begum, A. S., Hira, K., Niazi, S., Kumar B. R. P., Araya, H., & Fujimoto, Y. (2019). Structure-based design and synthesis of new 4-methylcoumarin-based lignans as pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) inhibitors. Bioorganic Chemistry, 89, 102991.

Kuppusamy, P., Soundharrajan, L., Kim, D. H., Hwang, I. H., & Choi, K. C. (2019). 4-hydroxy-3-methoxy cinnamic acid accelerate myoblasts differentiation on C2C12 mouse skeletal muscle cells via AKT and ERK 1/2 activation. Phytomedicine, 60, 152873.

Landberg, R., Sunnerheim, K., & Dimberg, L. H. (2020). Avenanthramides as lipoxygenase inhibitors. Heliyon, 6(6), e04304.

Lao, Z., & Toy, P. H. (2016). Catalytic Wittig and aza-Wittig reactions. Beilstein Journal of Organic Chemistry, 12, 2577−2587.

Mabeta, P., Pavić, K., & Zorc, B. (2018). Insights into the mechanism of antiproliferative effects of primaquine-cinnamic acid conjugates on MCF-7 cells. Acta Pharmaceutica, 68(3), 337−348.

Martínez-Soriano, P. A., Macías-Pérez, J. R., Velázquez, A. M., Camacho-Enriquez, B. C., Pretelín-Castillo, G., Ruiz-Sánchez, M. B., Abrego-Reyes, V. H., Villa-Treviño, S., & Angeles, E. (2015). Solvent-free synthesis of carboxylic acids and amide analogs of CAPE (caffeic acid phenethyl ester) under infrared irradiation conditions. Green and Sustainable Chemistry, 5(2), 81−91, 2015.

Medvedeva, M., Barinova, K., Melnikova, A., Semenyuk, P., Kolmogorov, V., Gorelkin, P., Erofeev, A., & Muronetz, V. (2020). Naturally occurring cinnamic acid derivatives prevent amyloid transformation of alphasynuclein. Biochimie, 170, 128 – 139.

Meeprom, A., Chan, C., Sompong, W., & Adisakwattana, S. (2018). Isoferulic acid attenuates methylglyoxal-induced apoptosis in INS-1 rat pancreatic β-cell through mitochondrial survival pathways and increasing glyoxalase-1 activity. Biomedicine & Pharmacotherapy, 101, 777−785.

Narasimhan, B., Belsare, D., Pharande, D., Mourya, V., & Dhake, A. (2004). Esters, amides and substituted derivatives of cinnamic acid: synthesis, antimicrobial activity and QSAR investigations. European Journal of Medicinal Chemistry, 39 (10), 827−834.

Nishikawa, K., Fukuda, H., Abe, M., Nakanishi, K., Taniguchi, T., Nomura, T., Yamaguchi, C., Hiradate, S., Fujii, Y., Okuda, K., & Shindo, M. (2013). Substituent effects of cis cinnamic acid analogues as plant growh Inhibitors. Phytochemistry, 96, 132−147.

Park, Y., Kim, S., Lyou, Y., Lee, J., & Yang, J. (2005). A new type of uncompetitive inhibition of tyrosinase induced by Cl– binding. Biochimie, 87(11), 931−937.

Passos, G. F. S., Gomes, M. G. M., Aquino, T. M., Araújo – Júnior, J. X., De Souza, S. J. M., Cavalcante, J. P. M., Dos Santos, E. C., Bassi, E. J., & Silva – Júnior, E. F. (2020). Computer aided design, synthesis, and antiviral evaluation of novel acrylamides as potential inhibitors of E3-E2-E1 glycoproteins complex from chikungunya virus. Pharmaceuticals, 13(7), 141.

Pawar, P. M., Jarag, K. J., & Shankarling, S. G. (2011). Environmentally benign and energy efficient methodology for condensation: an interesting facet to the classical Perkin reaction Green Chemistry, 13(8), 2130−2134.

Peperidou, A. Pontiki, E., Hadjipavlou-Litina, D., Voulgari, E., & Avgoustakis, K. (2017). Multifunctional cinnamic acid derivatives. Molecules, 22 (8), 1247.

Pereira, A. C., Carmo, E. D., Silveira, V. A. S., Amadei, S. U., & Rosa, L. E. B. (2006). O papel das MMP-2 e -9 no desenvolvimento do carcinoma epidermóide. Revista Brasileira de Cancerologia, 52(3), 257-262.

Pereira, A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica. Santa Maria: Núcleo de Tecnologia Educacional da Universidade Federal de Santa Maria.

Pontiki, E., Hadjipavlou-Litina, D., Litinas, K., & Geromichalos, G. Molecules. (2014). Novel cinnamic acid derivatives as antioxidante and anticâncer agents: design, synthesis and modeling studies, 19 (7), 9655−9674.

Procópio, T. F., Fernandes, K. M., Pontual, E. V., Ximenes, R. M., Oliveira, A. R. C., Souza, C. S., Melo, A. M. M. A., Navarro, D. M. A. F., Paiva, P. M. G., Martins, G. F., & Napoleão, T. H. (2015). Schinus terebinthifolius leaf extract causes Midgut damage, interfering with survival and development of Aedes aegypti larvae. PLOS ONE, 10(5), 1−19.

Rastogi, N., Domadia, P., Shetty, S., & Dasgupta, D. (2008). Screening of natural phenolic compounds for potential to inhibit bacterial cell division protein FtsZ. Indian Journal of Experimental Biology, 46(11), 783–787.

Rathee, D., Lather, V., Grewal, A. S., & Dureja, H. (2018). Targeting matrix metalloproteinases with novel diazepine substituted cinnamic acid derivatives: design, synthesis, in vitro and in silico studies. Chemistry Central Journal, 12(1), 1−15.

Ren, G., Cui, X., Yang, E., Yang, F., & Wu, Y. (2010). Study on the Heck reaction promoted by carbene adduct of cyclopalladated ferrocenylimine and the related reaction mechanism Tetrahedron, 66(23), 4022−4028.

Rodrigues, M. P., Tomaz, D. C., Souza, L. A., Onofre, T. S., Menezes, W. A., Almeida-Silva, J., Ana Marcia Suarez-Fontes, A. M., Almeida, M. R., Silva, A. M., Bressan, G. C., Vannier-Santos, M. A., Fietto, J. L. R., & Teixeira, R. R. (2019). Synthesis of cinnamic acid derivatives and leishmanicidal activity against Leishmania braziliensis. European Journal of Medicinal Chemistry, 183, 111688.

Rowinsky, E. K., Windle, J. J., & Hoff, D. D. V. (1999). Ras Protein Farnesyltransferase: A Strategic Target for Anticancer Therapeutic Development. Biology of Neoplasia, 17(11), 3631−3652.

Saito, M. L., & Lucchini, F. (1997). Substancias do metabolismo secundário de plantas no controle de pragas agrícolas. LECTA, Bragança Paulista. LECTA, Bragança Paulista, 15(1/2), 211−245.

Sano, S., Takemoto, Y., & Nagao, Y. (2007). (E)-Selective Horner–Wadsworth–Emmons reaction of aldehydes with bis-(2,2,2-trifluoroethyl) phosphonoacetic acid Archive for Organic Chemistry, 8, 93−101.

Saurabh Pagare, S., Bhatia, M., Tripathi, N., Pagare, S., & Bansal, Y. K. (2015). Secondary metabolites of plants and their role: overview. Current Trends in Biotechnology and Pharmacy, 9(3), 293 – 304.

Sharma, P. (2011). Cinnamic acid derivatives: A new chapter of various pharmacological activities. Journal of Chemical and Pharmaceutical Research, 3 (2), 403−423.

Shi, Z., Li, N., Shi, Q., Tang, H., & Tang, Y. (2012). Design, synthesis, and preliminary evaluation of substituted cinnamic acid esters as selective matrix metalloproteinase inhibitors. Drug Development Research, 73 (6), 317−324.

Sova, M., Turk, S., Stankovic, J., & Juranic, J. (2013). Cinnamic acid derivatives induce cell cycle arrest in carcinoma cell lines. Medicinal Chemístry, 9 (5), 633−641.

Su, Y., Wua, Z., & Tian, S. (2013). Oxidative alkoxycarbonylation of terminal alkenes with carbazates. Chemical Communications, 48 (58), 6528−6530.

Teixeira, C., Ventura, C., Gomes, J. R. B., Gomes, P., & Martins, F. (2020). Cinnamic derivatives as antitubercular agents: characterization by quantitative structure–activity relationship studies. Molecules, 25 (3), 456.

Tonari, K., Mitsui, K., & Yonemoto, K. (2002). Structure and antibacterial activity of cinnamic acid related compounds. Journal of Oleo Science, 51(4), 271–273.

Untura, L. P., & Rezende, L. F. (2012). A função cognitiva em pacientes submetidos à quimioterapia: uma revisão integrativa. Revista Brasileira de Cancerologia, 58(2), 257 – 265.

Vogt, T. (2010). Phenylpropanoid Biosynthesis. Molecular Plant, 3(1), 2−20.

Wadsworth, W. S., & Emmons, W. D. (1961). The utility of phosphonate carbanions in olefin synthesis. J. Amer. Chem. Soc, 83(7), 1733−1738.

Wang, Y., Du, G., Gu, C., Xing, F., Dai, B., & He, L. (2016). N-heterocyclic carbene-catalysed Peterson olefination reaction. Tetrahedron, 72(4), 472− 478.

Weiner, B. (2009). New Methods towards the synthesis of beta-amino acids. University of Groningen.

Zeng, W. W., & Lai, L. S. (2019). Multiple-physiological benefits of bird’s nest fern (Asplenium australasicum) frond extract for dermatological applications. Natural Product Research, 33 (5), 736-741.

Zhang, J., Hao, W., Zhorov, B., Dong, K., & Jiang, D. (2019). Discovery of a Novel Series of Tricyclic Oxadiazine 4a-Methyl Esters Based on Indoxacarb as Potential Sodium Channel Blocker/ Modulator Insecticides. Agriculture and Food Chemistry, 67(28), 7793−7809.

Zhang, W. X., Wang, H., Cui, H. R., Guo, W. B., Zhou, F., Cai, D. S., Xu, B., Jia, X. H., Huang, X. M., Yang, Y. Q., Chen, H. S., Qi, J. C., Wang, P. L., & Lei, H. M. (2019). Design, synthesis and biological evaluation of cinnamic acid derivatives with synergetic neuroprotection and angiogenesis effect. European Journal of Medicinal Chemistry, 183(1), 111695.

Published

13/01/2021

How to Cite

FRANÇA, S. B.; CORREIA, P. R. dos S.; CASTRO, I. B. D. de; SILVA JÚNIOR, E. F. da; BARROS, M. E. de S. B.; LIMA, D. J. da P. Synthesis, applications and Structure-Activity Relationship (SAR) of cinnamic acid derivatives: a review. Research, Society and Development, [S. l.], v. 10, n. 1, p. e28010111691, 2021. DOI: 10.33448/rsd-v10i1.11691. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/11691. Acesso em: 8 mar. 2021.

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Section

Exact and Earth Sciences