The present study was designed to carry out the synthesis of targeted N-arylindole imines (derived from 4,5,6-trimethoxy-2,3-diphenyl-1H-indole-7-carbaldehyde), their characterization by spectroscopic and spectrometric methods, and evaluation of gastroprotector activity. The gastroprotective potential of indole imines (5 – 10) was elucidated after peroral administration of compounds in various doses to h EtOH-induced and indomethacin-induced gastric ulcers. In order to determine the mechanism of drug action, the effects of compounds on pH, ulcer index, gastric volume, gastric mucus content, and antioxidant biomarkers were determined. Among five newly synthesized compounds, two halogen derivatives (8 and 9) showed significant protection at 40 and 60 mg/kg doses as compared to standard drug omeprazole. In EtOH-induced gastric ulcer model, indole imine 9 significantly increased the mucus content. Both compounds (8 and 9) were found to attenuate the formation of gastric lesions in indomethacin-induced ulcer model. The serum values of antioxidant biomarkers revealed promising increase in total antioxidant status by compounds 8 and 9. The obtained results suggest the synthetic indole imines 8 and 9 to be remarkable gastroprotective compounds capable of modulating oxidative stress.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
H. D. S. Falco, J. A.Leite, J. M. Barbosa-Filho, et al., Molecule, 13(12), 3198 – 3223. (2008).
J. U. Park, J. H. Kang , M. A. Rahman, et al., BioMed Res. Intern., 2019.
A. Zolezzi, Rev Gastroenterol Peru, 18, 44 – 55 (1998).
H. M Spiro, Pharmacotherapy, 2(2), 67 – 71 (1982).
D. E. Butler, R. A. Purdon, and P. Bass, Am. J. Dig. Dis., 15(2), 157 – 170 (1970).
T. Kawamura, A. Torii, H .Nozawa, et al., ExcerptaMedica (Amsterdam), 48 – 60 (1985).
A. Ariyoshi, F. Toshihara, M. Sugimura, et al., Folia Pharmacol., 87, 551 (1986).
S. P. Shraddha and R. D. Kamlesh, IJRPC, 6(2), 301 – 311 (2016).
R. Malcolm, A. W. Zalay, R. Oesterlin, et al., J. Med. Chem., 20, 537 (1977).
H. Tokuyama, S. Yokoshima, T. Yamashita, and T. Fukuyama, Tetrahedron Lett, 39(20), 3189 – 3192 (1998).
A. D. Batcho and W. Leimgruber, Org. Synth., 63, 214 – 220 (1985).
B. Robinson, Chem. Rev., 69(2), 227 – 250 (1969).
K. Karakaya, F. Barut, and V. Hanci, Bratisl. Lek Listy, 116(1), 51 – 56. (2015).
N. Poornima, P. Revathi, and T. Parimelazhagan, J. Food Drug Anal., 23(3), 376 – 386 (2015).
B. A. Michael, A. Charles, G. Isaac, et al., Ulcer Agents. Ulcers, 1(2), 12 (2013).
S. J. Corne and S. M. Morrissey, J. Physiol., 242, 116 – 117 (1974).
N. A. Konan, E. M. Bacchi, N. Lincopan, et al., J. Ethnopharmacol., 110(1), 30 – 38 (2007).
M. Lee, S. M. Kallal, and M. Feldma, Aliment Pharmacol Ther., 10(4), 571 – 576 (1996).
P. Govind and J. Saurabh, Res. J. Pharmacol., 4, 66 – 68 (2010).
O. Erel, Clin. Biochem., 38, 1103 – 1111 (2005).
M. S. Blois, Nature, 26, 1199 – 1200 (1958).
D. St. C. Black, B. M. K. C. Gatehouse, F. Theobald, and L. C. H. Wong, Aust. J. Chem., 33, 343 – 350 (1980).
D. St. C. Black, N. Kumar, and L. C. H. Wong, Aust. J. Chem., 39, 15 – 20 (1986).
D. St. C. Black, M. C. Bowyer, P. K. Bowyer, et al., Aust. J. Chem., 47, 1741 – 1750 (1994).
A. Vilsmeier and A. Haack, Chem. Ber., 60, 199 (1927).
I. A. Al-Mofleh, A. A. Alhaider, J. S. Mossa, et al., Saudi J. Gastroenterol., 14(3), 128 – 134 (2008).
F. E. Júnior, D. R. Oliveira, and A. A. Boligon, J. Ethnopharmacol., 153(2), 469 – 477 (2014).
S. Vedavyasa, Indian J. Exp. Biol., 37, 365 – 369 (1999).
P. Muralidharan and J. Srikanth, J. Sci. Res., 1(2), 345 – 352 (2009).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Akhtar, M.S., Raza, A.R., Aziz, M. et al. Synthesis and Gastroprotective Evaluation of New Synthetic Indole Imines on Animal Models. Pharm Chem J 54, 26–35 (2020). https://doi.org/10.1007/s11094-020-02150-w
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11094-020-02150-w