Synthesis, in-vitro antioxidant and anti-inflammatory properties of novel amide derivatives of substituted 2-aminothiophenes and 3,4-dimethoxy cinnamic acid

Satya Sree Bandaru Madhavi Kuchana   

Open Access   

Published:  Apr 09, 2024

DOI: 10.7324/JAPS.2024.180925
Abstract

Novel amide derivatives using substituted 2-aminothiophenes (1A–12A) were synthesized by following a suitable procedure. The synthesized compounds were characterized by physical and spectral data. The compounds were screened for in-vitro antioxidant and anti-inflammatory activities with reference to the standard drugs, Ascorbic acid and Ibuprofen respectively. The majority of the compounds showed good antioxidant activity in DPPH and hydroxyl radical scavenging assays. The synthesized compounds were also tested for in-vitro anti-inflammatory activity by protein denaturation and HRBC membrane stabilization methods. Among all, the compounds 2A and 3A showed significant in-vitro anti-inflammatory activity when compared with the standard drug Ibuprofen.


Keyword:     3 4-Dimethoxy cinnamic acid tranilast substituted 2-aminothiophenes amide derivatives antioxidant anti-inflammatory


Citation:

Bandaru SS, Kuchana M. Synthesis, in-vitro antioxidant and anti-inflammatory properties of novel amide derivatives of substituted 2-aminothiophenes and 3,4-dimethoxy cinnamic acid. J Appl Pharm Sci. 2024. Online First. http://doi.org/10.7324/JAPS.2024.180925

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

1. Gewald K, Schinke E, Bottcher H. 2-Amino-thiophene aus methylenaktiven Nitrilen, Carbonylverbindungen und Schwefel. ChemBer. 1966;(99):94–100. doi: https://doi.org/10.1002/cber.19660990116

2. Priyanka SC, Sohan SC, Rabindra K. Molecular docking, synthesis and anti-inflammatory activity of some tetrasubstituted thiophene derivatives. Int Res J Pharm. 2018;9(6):163–9. doi: https://doi.org/10.7897/2230-8407.096110

3. Mahdavi B, Hosseyni?Tabar SM, Rezaei?Seresh E, Rezaei-Seresht H, Falanji F. Synthesis and biological evaluation of novel hybrid compounds derived from gallic acid and the 2-aminothiophene derivatives. J Iran Chem Soc. 2020;(17):809–15. doi: https://doi.org/10.1007/s13738-019-01813-0

4. Madhavi K, Ramanamma KV. Synthesis and evaluation of ethyl 2-(2-cyano-3-(substituted phenyl)acrylamido)-4, 5, 6, 7-tetrahydrobenzo[b]thiophene-3-carboxylates for antioxidant and antibacterial activities. Int J Curr Microbiol Appl Sci. 2016;5(1):364–75. doi: https://doi.org/10.20546/ijcmas.2016.501.034

5. Asiri YI, Muhsinah AB, Alsayari A, Venkatesan K, Al-Ghorbani M, Mabkhot YN. Design, synthesis and antimicrobial activity of novel 2-aminothiophene containing cyclic and heterocyclic moieties. Bioorganic Med Chem Lett. 2021;(44):128117–22. doi: https://doi.org/10.1016/j.bmcl.2021.128117

6. Thomas J, Jecic A, Vanstreels E, Berckelaer LV, Romagnoli R, Dehaen W, Liekens S, Balzarini J. Pronounced anti-proliferative activity and tumor cell selectivity of 5-alkyl-2-amino-3-methylcarboxylate thiophenes. Eur J Med Chem. 2017;(132):219–35. doi: https://doi.org/10.1016/j.ejmech.2017.03.044

7. Rodrigues KADF, Dias CNDS, Neris PLDN, Rocha JDC, Scotti MT. 2-Amino thiophene derivatives present antileishmanialactivity mediated by apoptosis and immunomodulation in vitro. Eur J Med Chem. 2015;(106):1–14. doi: https://doi.org/10.1016/j.ejmech.2015.10.011

8. Kunda PK, Rao JV, Mukkanti K, Induri M, Reddy GD. Synthesis, anticonvulsant activity and in-silico studies of schiff bases of 2-aminothiophenes via guanidine-catalyzed Gewald reaction. Trop J Pharm Res. 2013;12(4):566–76. doi: https://doi.org/10.4314/tjpr.v12i4.19

9. Ibrahim BA, Mohareb RM. Uses of ethyl benzoyl acetate for the synthesis of thiophene, pyran, and pyridine derivatives with antitumor activities. J Heterocycl Chem. 2020;(57):4023–35. doi: https://doi.org/10.1002/jhet.4112.

10. Shimada O, Yasuda H. Hydroxyl radical scavenging action of tinoridine. Agents Actions. 1986;19(3-4):208–14. doi: https://doi.org/10.1007/BF01966208

11. Tuzun S, Uzun H, Aydin S, Dinc A, Sipahi S, Topcuoglu MA et al. Effect of flubiprofen and tiaprofenic acid on oxidative stress markers in osteoarthritis: a prospective, randomized, open label, active and placebo-controlled trial. Curr Therap Res. 2005;66(5):335–44. doi: https://doi.org/10.1016/j.curtheres.2005.08.002

12. Lau CS, Belch JJF. The in vitro free radical scavenging activity of tenidap, a new dual cyclo-oxygenase and 5-1ipoxygenase inhibitor. Mediators Inflamm. 1992;(1):141–3. doi: https://doi.org/10.1155/S0962935192000231

13. Andrade PB, Leitao R, Seabra RM, Oliveira MB, Ferreira MA. 3,4-Dimethoxycinnamic acid levels as a tool for differentiation of Coffea canephora var. robusta and Coffea arabica. Food Chem. 1998;61(4):511–4. doi: https://doi.org/10.1016/S0308-8146(97)00067-8.

14. Nobelos PT, Papagiouvannis G and Rekka EA. Ferulic, sinapic, 3,4-dimethoxycinnamic acid and indomethacin derivatives with antioxidant, anti-inflammatory and hypolipidemic functionality. Antioxidants. 2023;12(7):1436–51. doi: https://doi.org/10.3390/antiox12071436.

15. De P, Baltas M, Belval FB. Cinnamic acid derivatives as anticancer agents-a review. Curr Med Chem. 2011;18(11):1672–703. doi: https://doi.org/10.2174/092986711795471347.

16. Ling Y, Gao WJ, Ling C, Liu J, Meng C, Qian J, et al. β-Carboline and N-hydroxy cinnamamide hybrids as anticancer agents for drug-resistant hepatocellular carcinoma. Eur J Med Chem. 2019;(168):515–26. doi: https://doi.org/10.1016/j.ejmech.2019.02.054.

17. Chen L, Zhao B, Fan Z, Hu M, Li Q, Hu W, et al. Discovery of novel isothiazole, 1,2,3-thiadiazole, and thiazole-based cinnamamides as fungicidal Candidates. J Agric Food Chem. 2019;67(45):12357–65. doi: https://doi.org/10.1021/acs.jafc.9b03891.

18. Sova M. Antioxidant and antimicrobial activities of cinnamic acid derivatives. Mini Rev Med Chem. 2012;12(8):749–67. doi: https://doi.org/10.2174/138955712801264792

19. Lan JS, Hou JW, Liu Y, Ding Y, Zhang Y, Li L, et al. Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer’s disease. J Enzyme Inhib Med Chem. 2017;32(1):776–8. doi: https://doi.org/10.1080/14756366.2016.1256883

20. Darakhshan S, Pour AB. Tranilast: a review of its therapeutic applications. Pharmacol Res. 2015;(91):15–28. doi: https://doi.org/10.1016/j.phrs.2014.10.009

21. Josue SBF, Erika MC, Joel JJ, Flavia MS. A new protocol for the synthesis of 2-aminothiophenes through the Gewald reaction in solvent-free conditions. Heterocycl Let. 2011;1(1):61–7. doi: https://doi.org/http://www.heteroletters.org

22. Haswani NG, Sanjaykumar BB. Synthesis and antimicrobial activity of novel 2-(pyridin -2-yl)thieno[2,3-d]pyrimidin-4 (3H)-ones. Turk J Chem. 2011;35(6):915–24. doi: https://doi.org/10.3906/kim-1012-888

23. Durgareddy GANK, Ravikumar R, Ravi S, Srinivas RA. A CaO catalyzed facile one pot synthesis of 2-aminothiophenes usingGewald reaction. Der Pharma Chemica. 2013;5(6):294–8. doi: http://derpharmachemica.com/archive.html

24. Gangadhara S, Prasad Ch, Venkateswarlu P. Synthesis, antimicrobial and antioxidant activities of novel series of cinnamamide derivatives having morpholine moiety. Med Chem. 2014;4(12):778–83. doi: https://doi.org/10.4172/2161-0444.1000229

https://doi.org/10.4172/2161-0444.1000229

25. Jitareanu A, Tataringa G, Zbancioc AM, Tuchilus C, Balan M, Stanescu U. Cinnamic acid derivatives and 4-aminoantipyrine amides–synthesis and evaluation of biological properties. Res J Chem Sci. 2013;3(3):9–13. Available from: http://www.isca.in

26. Madhavi K, Swathi K, Anitha B, Sree GRU, Sravanthi G, Ashwini G. Synthesis and evaluation of novel α-cyano-N-(4-hydroxyphenyl)cinnamamides for antioxidant, anti-inflammatory activities: in-silico prediction of drug likeness properties. Int J Pharm Sci Res. 2019;10(1):203–13. doi: https://doi.org/10.13040/IJPSR.0975-8232.10(1).203-13

27. Kumar BS. Phytochemical screening and antioxidant properties of methanolic extract of root of Asparagus racemosus Linn. Int J Food Prop. 2018;21(1):2681–8. doi: https://doi.org/10.1080/10942912.2018.1560310

28. Kar B, Kumar RS, Karmakar I, Dola N, Bala A, Mazumder UK, et al. Antioxidant and in vitro anti-inflammatory activities of Mimusops elengi leaves. Asian Pac J Trop Biomed. 2012;(2):S976–80. doi: https://doi.org/10.1016/S2221-1691(12)60346-3.

29. Kumar V, Bhat ZA, Kumar D, Puja B, Sheela S. In-vitro anti-inflammatory activity of leaf extracts of Basella Alba linn. Var. Alba. Int J Drug Dev Res. 2011;3(2):176–9. Available from: http://www.ijddr.in.

30. Shahnaj PM, Nandita D, Nusrat J, Afia AM, Nahar L, Islam EM. Evaluation of in vitro anti-inflammatory and antibacterial potential of Crescentia cujete leaves and stem bark. BMC Res Notes. 2015;8:412–8. doi: https://doi.org/10.1186/s13104-015-1384-5

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