A THERAPEUTIC INSIGHTS ON EMERGING INDOLE-3-ACETIC ACID DERIVATIVES

Abstract

Objective: Auxin or indole-3-acetic acid (IAA) is a pivotal phytohormone that regulates plant growth, development, and environmental responses Indole-3-acetic acid (IAA), a small molecule originated early in evolution in organisms like blue-green algae (cyanobacteria). Structurally, IAA consists of a carboxylic side chain and an indole ring. IAA exhibits unique biological behaviors such as dimer formation stabilized by hydrogen bonding. It is synthesized by plants and certain bacteria including Pseudomonas, Rhizobium and Azospirillum, through complex, redundant biosynthetic pathways involving multiple intermediates and enzymes. These pathways demonstrate robustness and adapt ability, enabling compensation for disruptions. The indole-3-acetic acid derivatives were designed and studied numerously for their wide array of pharmacological actions. Therefore, derivatives of this moiety need to be studied for the identification of their diverse pharmacological actions, which will help the future medicinal chemists to a larger extent.

Result and Discussion: In this review study, the different derivatives of Indole-3-acetic acid were studied. The study highlights the synthetic and medicinal potential of indole-3-acetic acid and its indole-based analogues, exploring their role in advancing therapeutic and biological applications.

Keywords

• Anticancer
• antidiabetic
• antimicrobial
• antioxidant
• indole-3-acetic acid

Project Number

0

Ethical Statement

There is no human or animal subject were utilized while carrying out this study.

İNDOL-3-ASETİK ASİT TÜREVLERİ HAKKINDA TERAPÖTİK BİR BAKIŞ AÇISI

Abstract

Amaç: Oksin veya indol-3-asetik asit (IAA), bitki büyümesini, gelişimini ve çevresel tepkileri düzenleyen temel bir fitohormondur İndol-3-asetik asit (IAA), mavi-yeşil algler (siyanobakteriler) gibi organizmalarda evrimin erken dönemlerinde ortaya çıkan küçük bir moleküldür. Yapısal olarak, IAA bir karboksilik yan zincir ve bir indol halkasından oluşur. IAA, hidrojen bağıyla stabilize edilen dimer oluşumu gibi benzersiz biyolojik davranışlar sergiler. Bitkiler ve Pseudomonas, Rhizobium ve Azospirillum dahil olmak üzere belirli bakteriler tarafından, birden fazla ara ürün ve enzim içeren karmaşık, yedekli biyosentetik yollarla sentezlenir. Bu yollar, bozulmaların telafi edilmesini sağlayan sağlamlık ve uyum yeteneği gösterir. İndol-3-asetik asit türevleri, çok çeşitli farmakolojik etkileri için sayısız kez tasarlanmış ve incelenmiştir. Bu nedenle, bu grubun türevlerinin çeşitli farmakolojik etkilerinin belirlenmesi için incelenmesi gerekmektedir; bu, geleceğin tıbbi kimyacılarına daha büyük ölçüde yardımcı olacaktır.

Sonuç ve Tartışma: Bu derleme çalışmasında, İndol-3-asetik asidin farklı türevleri incelendi. Çalışma, indol-3-asetik asidin ve indol bazlı analoglarının sentetik ve tıbbi potansiyelini vurgulayarak, terapötik ve biyolojik uygulamaları ilerletmedeki rollerini araştırmaktadır.

Keywords

• Antidiyabetik
• antikanser
• antimikrobiyal
• antioksidan
• indol-3-asetik asit

Project Number

0

References

1. 1. Hager, A. (2003). Role of the plasma membrane H+-ATPase in auxin-induced elongation growth: Historical and new aspects. Journal of Plant Research, 483-505.[CrossRef]
2. 2. Duca, D., Lorv, J., Patten, C.L., et al. (2014). Indole-3-acetic acid in plant-microbe interactions. International Journal of General and Molecular Microbiology, 106, 85-125. [CrossRef]
3. 3. Sergeeva, E., Liaimer, A., Bergman, B. (2002). Evidence for production of the phytohormone indole-3-acetic acid by cyanobacteria. Planta, 215(2), 229-38. [CrossRef]
4. 4. Kiralj, R., Ferreira, M.M.C. (2005). Chemometric and molecular modeling study of 1H-indole-3-acetic acid derivatives with auxin activity. Croatia Chemica Acta, 78(4), 541-9.
5. 5. Tromas A., Perrot-Rechenmann C. (2010). Recent progress in auxin biology. Comptes Rendus Biologies, 333(4), 297-306. [CrossRef]
6. 6. Ahn, Y.Y., Bagrow, J.P., Lehmann, S. (2010). Link communities reveal multiscale complexity in networks. Nature, 466(7307), 761-4. [CrossRef]
7. 7. Soeno, K., Goda, H., Ishii, T., et al. (2010). Auxin biosynthesis inhibitors, identified by a genomics-based approach, provide insights into auxin biosynthesis. Plant and Cell Physiology, 51(4), 524-36. [CrossRef]
8. 8. Schütz, A., Golbik, R., Tittmann, K., et al. (2003). Studies on structure-function relationships of indolepyruvate decarboxylase from Enterobacter cloacae, a key enzyme of the indole acetic acid pathway. European Journal of Biochememistry, 270(10), 2322-31. [CrossRef]

9. 9. Koga, J., Adachi, T., Hidaka, H. (1992). Purification and characterization of indolepyruvate decarboxylase. A novel enzyme for indole-3-acetic acid biosynthesis in Enterobacter cloacae. Journal of Biological Chemistry. 267(22), 15823-8. [CrossRef]
10. 10. Johnson, H.E., Crosby, D.G. (1964). Indole-3-acetic acid. Organic Syntheses, 44, 64. [CrossRef]
11. 11. Dou, L., Sallée, M., Cerini, C., et al. (2015). The cardiovascular effect of the uremic solute indole-3 acetic acid. Journal of the American Society of Nephrology, 26(4), 876-87. [CrossRef]
12. 12. Salehi, B., Martorell, M., Arbiser, J.L., et al. (2018). Antioxidants: Positive or negative actors? Biomolecules, 8, 124. [CrossRef]
13. 13. Kanwal, Khan, K.M., Chigurupati, S., Ali, F., et al. (2021). Indole-3-acetamides: As potential antihyperglycemic and antioxidant agents; synthesis, in vitro α-amylase inhibitory activity, structure-activity relationship, and in silico studies. ACS Omega, 6(3), 2264-75. [CrossRef]
14. 14. Saija, A., Scalese, M., Lanza, M., et al. (1995) Brief Communication flavonoids as antioxidant agents: Importance of their interaction with biomembranes. Free Radical Biology Medicine, 19(4), 481-486. [CrossRef]
15. 15. Ölgen, S., Kiliç, Z., Ada, A.O., et al. (2007). Synthesis and antioxidant properties of novel N-H and N-substituted propanamide derivatives. Chemistry in Life Sciences, 340(3), 140-6. [CrossRef]
16. 16. Pinna, G.A., Pirisi, M.A., Sechi, M., et al. (1998). Synthesis and in vitro anticancer activity evaluation of biscarbamic esters of 2,3-bis(hydroxymethyl)-1-methyl-7-and 7-substituted-benzo[g]indoles. Il Farmaco, 53. 161-168. [CrossRef]
17. 17. Javaid, M., Haq, I.U., Nadeem, H., et al. (2023). Design, synthesis and screening of indole acetic acid-based tri-azo moieties as antioxidants, anti-microbial and cytotoxic agents. Frontiers in Pharmacology, 14, 1084181. [CrossRef]
18. 18. Kudličková, Z., Michalková, R., Salayová, A., et al. (2023). Design, synthesis, and evaluation of novel indole hybrid chalcones and their antiproliferative and antioxidant activity. Molecules, 28(18), 6583. [CrossRef]
19. 19. Naik, N., Kumar, H.V., Harini, S.T. (2011). Synthesis and antioxidant evaluation of novel indole-3-acetic acid analogues. European Journal of Chemistry, 2(3), 337-41. [CrossRef]
20. 20. Payne, D.J., Gwynn, M.N., Holmes, D.J., et al. (2007). Drugs for bad bugs: Confronting the challenges of antibacterial discovery. Nature Reviews Drug Discovery, 6, 29-40. [CrossRef]
21. 21. Bush, K., Bradford, P.A. (2016). β-lactams and β-lactamase inhibitors: An overview. Cold Spring Harbor Perspectives in Medicine, 6(8), a025247. [CrossRef]
22. 22. Sikandar K.N., Munawar K.S., Ahmad, T., et al. (2020). Synthesis, spectroscopic characterization and antibacterial screening of Zn(II), Cu(II) and VO(IV) complexes derived from indole-3-acetic acid. Lahore Garrison University Journal of Life Sciences, 4(3), 209-26. [CrossRef]
23. 23. Cadelis, M.M., Li, S.A., Bourguet-Kondracki, M.L., et al. (2021). Spermine derivatives of indole-3-carboxylic acid, indole-3-acetic acid and indole-3-acrylic acid as gram-negative antibiotic adjuvants. ChemMedChem,16(3), 513-23. [CrossRef]
24. 24. Choppara, P., Bethu, M.S., Prasad, Y.V., et al. (2019). Synthesis, characterization and cytotoxic investigations of novel bis(indole) analogues besides antimicrobial study. Arabian Journal of Chemistry, 12(8), 2721-31. [CrossRef]
25. 25. Munhoz, A.C.M., Frode, T.S. (2017). Isolated compounds from natural products with potential antidiabetic activity - a systematic review. Current Diabetes Reviews, 14(1), 36-106. [CrossRef]
26. 26. Khan, S., Iqbal, T., Khan, Y., et al. (2024). Experimental and computational pharmacological approaches decoding the anti-diabetic molecular mechanism of indole based triazole bearing sulfonothioate derivatives. Results in Chemistry, 10, 101707. [CrossRef]
27. 27. Nazir, M., Abbasi, M.A., Aziz-ur-Rehman, Siddiqui, S.Z., et al. (2018). New indole-based hybrid oxadiazole scaffolds with N-substituted acetamides: As potent anti-diabetic agents. Bioorganic Chemistry, 81, 253-63. [CrossRef]
28. 28. Thanikachalam, P.V., Maurya, R.K., Garg, V., et al. (2019). An insight into the medicinal perspective of synthetic analogs of indole: A review. European Journal of Medicinal Chemistry, 180, 562-612. [CrossRef]
29. 29. Nomura, S., Yamamoto, Y., Matsumura, Y., et al. (2014). Novel indole-N-glucoside, TA-1887 As a sodium glucose cotransporter 2 inhibitor for treatment of type 2 diabetes. ACS Medicinal Chemistry Letters, 5(1), 51-5. [CrossRef]
30. 30. Vaddiraju, N., Ajitha, M., Rajnarayana, K. (2021). Synthesis, characterization and evaluation of antidiabetic activity of novel pyrazoline fused indole derivatives. Journal of Pharmaceutical Research International, 33(52B), 276-92. [CrossRef]
31. 31. Xu, Q., Huang, L., Liu, J., et al. (2012). Design, synthesis and biological evaluation of thiazole- and indole-based derivatives for the treatment of type II diabetes. European Journal of Medicinal Chemistry, 52, 70-81. [CrossRef]
32. 32. Lamotte, Y., Martres, P., Faucher, N., et al. (2010). Synthesis and biological activities of novel indole derivatives as potent and selective PPARγ modulators. Bioorganic Medicinal Chemistry Letters, 20(4), 1399-404. [CrossRef]
33. 33. Sashidhara, K.V., Kumar, A., Kumar, M., et al. (2010). Synthesis and in vitro evaluation of novel coumarin-chalcone hybrids as potential anticancer agents. Bioorganic Medicinal Chemistry Letters, 20(24), 7205-11. [CrossRef]
34. 34. Zahoor, AF., Saeed, S., Rasul, A., et al. (2023). Synthesis, cytotoxic, and computational screening of some novel indole-1,2,4-triazole-based S-alkylated N-aryl acetamides. Biomedicines, 11(11), 3027. [CrossRef]
35. 35. Anantoju, K.K., Bireddy, S.R., Eppakayala, L., et al. (2024). An efficient synthesis and anticancer evaluation of 1,2,3-triazolo-indole-2-carboxylate derivatives. Results in Chemistry, 7, 101536. [CrossRef]
36. 36. Frederich, M., Tits, M., Angenot, L. (2008). Potential antimalarial activity of indole alkaloids. Transactions of the Royal Society of Tropical Medicine and Hygiene, 102, 11-9. [CrossRef]
37. 37. Rassbach, J., Hilsberg, N., Haensch, V.G., et al. (2023) Non-canonical two-step biosynthesis of anti-oomycete indole alkaloids in Kickxellales. Fungal Biology and Biotechnology, 10, 19. [CrossRef]
38. 38. Mathada, B.S., Somappa, S.B. (2022). An insight into the recent developments in anti-infective potential of indole and associated hybrids. Journal of Molecular Structure, 1261, 132808. [CrossRef]
39. 39. Yadav, R.R., Khan, S.I., Singh, S., et al. (2015). Synthesis, antimalarial, and antitubercular activities of meridianin derivatives. European Journal of Medicinal Chemistry, 98, 160-9. [CrossRef]
40. 40. Fernandez L.S., Buchanan, M.S., Carroll, A.R., et al. (2009). Antimalarial bis-indole alkaloids from Flindersia species. Organic Letters, 11(2), 329-32. [CrossRef]