Document Type : Original Article

Authors

1 Organic Chemistry Research Laboratory, Maharashtra Udaygiri Mahavidyalay, Udgir-413517, Maharashtra, India

2 School of Science, Navrachana University, Vasna-Bhayli Main Road, Bhayli, Vadodara-391410, Gujarat, India

Abstract

Thiazolidin-4-one derivatives have been hailed as “wonder nucleus” due to their profound biological activities. A number of derivatives with variable functional groups attached to the five-membered heterocyclic ring have been synthesized and further subjected to molecular docking studies, against C-KIT Tyrosine kinase target protein (1T46). The interactions, binding and affinity variations due to differences in functional groups have been studied using ChemDraw Ultra 7.0, RCSB – Protein Data Bank, BIOVIA Discovery Studio Visualizer 2021, MGL AutoDock Tools, AutoDock Vina and Vina Split software. The docking studies showed good interaction of the synthesized molecules with the 1T46 target protein. The ADME studies of these molecules have also been studied to identify which of the synthesized molecules have the potential to cross the Human Intestinal lining, as well as the BBB barrier. Out of the 18 molecules studied, 12 of them showed good potential to be absorbed by the intestine out of which only one molecule was able to show potential to cross the BBB barrier. There were 5 molecules that could not cross both the barrier. These studies could reveal which functionalities present attached to the thiazolidine-4-one could assist in human intestinal absorption and the crossing of the BBB barrier.

Graphical Abstract

In silico molecular docking against-KIT Tyrosine Kinase and ADME studies of 4-thiazolidinone derivatives

Keywords

Main Subjects

[1] Lengauer, M. Rarey, Curr. Opin. Struct. Biol., 1996, 6, 402–406. [Crossref], [Google Scholar], [Publisher]
[2] D. Taylor, P.J. Jewsbury, J.W. Essex, J. Comput. Aided Mol. Des., 2002, 16, 151–166. [Crossref], [Google Scholar], [Publisher]
[3] Z. Ghodsi, S. Roshankar, F. Mohajer, A. Badiei, H.K. Maleh, S.V. Gaikwad, Environ. Res., 2022, 12, 113245. [Crossref], [Google Scholar], [Publisher]
[4]A. Attique, M. Hassan, M. Usman, R.M. Atif, S. Mahboob, K.A. Al-Ghanim, M. Bilal, M.Z. Nawaz, Int. J. Environ. Res. Public Health, 2019, 16, 1–17. [Crossref], [Google Scholar], [Publisher]
[5]Gaikwad, S. Gaikwad, R. Kamble, J. Med. Chem. Sci., 2022, 5, 239-248. [Crossref], [Google Scholar], [Publisher]
[6] Gaikwad M. Gaikwad, P. Lokhande, Eurasian Chem. Commun., 2020, 2, 945-952. [Crossref], [Google Scholar], [Publisher]
[7] J.R. Yunta, American Journal of Modeling and Optimization, 2016, 4, 74–114. [Crossref], [Google Scholar], [Publisher]
[8] Pantsar, A. Poso, Molecules, 2018, 23, 1899. [Crossref], [Google Scholar], [Publisher]
[9] Y. Meng, H.X. Zhang, M. Mezei, M. Cui, Curr Comput Aided Drug Des., 2011, 146–157. [Crossref], [Google Scholar], [Publisher]
[10] Kumar, S. Patil, M. Pharm, Hygeia. J. D. Med., 2017, 9, 3590. [Crossref], [Google Scholar], [Pdf]
[11] K. Jain, A. Vaidya, V. Kashaw, S.K. Agrawal, R.K. Ravichandran, Bioorg. Med. Chem., 2012, 20, 3378-3395. [Crossref], [Google Scholar], [Publisher]
[12] C. Tripathi, S. Ji, G. Naz, P. Kumar, A. Verma, Eur. J. Med. Chem., 2014, 72, 52–77. [Crossref], [Google Scholar], [Publisher]
[13] V. Diurno, A.A. Izzo, O. Mazzoni, A. Bolognese, F. Capasso, J. Pharm. Pharmacol., 1996, 48, 760–762. [Crossref], [Google Scholar], [Publisher]
[14] A. Chavan, N.R. Pai, Arkivoc, 2007, 16, 148–155. [Crossref], [Google Scholar], [Publisher]
[15] A.O. Abeed, M.S.K. Youssef, R. Hegazy, J. Braz. Chem. Soc., 2017, 28, 2054–2063. [Crossref], [Google Scholar], [Publisher]
[16] M. Jackson, B. Blass, K. Coburn, L. Djandjighian, G. Fadayel, A.J. Fluxe, S.J. Hodson, J.M. Janusz, M. Murawsky, J.M. Ridgeway, R.E. White, S. Wu, Bioorg. Med. Chem. Lett., 2007, 17, 282. [Crossref], [Google Scholar], [Publisher]
[17] V. Diurno, O. Mazzoni, E. Piscopo, A. Calignano, F. Giordano, A. Bolognese, J. Med. Chem., 1992, 35, 2910–2912. [Crossref], [Google Scholar], [Publisher]
[18] N. Gavade, V.L. Markad, K.M. Kodam, M.S. Shingare, D.V. Mane, Bioorg. Med. Chem. Lett., 2012, 22, 5075–5077. [Crossref], [Google Scholar], [Publisher]
[19] Türe, M. Ergül, A. Altun, İ. Küçükgüzel, Mol. Divers., 2021, 25, 1025-1050. [Crossref], [Google Scholar], [Publisher]
[20] A. Szychowski, M.L. Leja, D.V. Kaminskyy, U.E. Binduga, O.R. Pinyazhko, R.B. Lesyk, J. Gmiński, Chem.-Biol. Interact., 2017, 262, 46–56. [Crossref], [Google Scholar], [Publisher]
[21] Karali, N. Terzioglu, A. Gursoy, Arch. Pharm. Pharm. Med. Chem., 2002, 8, 374. [Crossref], [Google Scholar], [Publisher]
[22] P.M. Rahman, S. Mukhtar, W.H. Ansari, G. Lemiere, Eur. J. Med. Chem., 2005, 40, 173-184. [Crossref], [Google Scholar], [Publisher]
[23] Wang, Y. Zhao, G. Zhang, Y. Lv, N. Zhang, P. Gong, Eur. J. Med. Chem., 2011, 46, 3509-3518. [Crossref], [Google Scholar], [Publisher]
[24] A. Gouda, A.A. Abu-Hashem, Arch. Pharm. Chem. Life Sci., 2011, 11, 170-177. [Crossref], [Google Scholar], [Publisher]
[25] Havrylyuk, N. Kovach, B. Zimenkovsky, O. Vasylenko, R. Lesyk, Arch. Pharm. Chem. Life Sci., 2011, 344, 514. [Crossref], [Google Scholar], [Publisher]
[26] Senkardes, S. Kucukguzel, Mini Rev. Org. Chem., 2016, 13, 377–388. [Crossref], [Google Scholar], [Publisher]
[27] K. Rawal, Y.S. Prabhakar, S.B. Katti, E. De Clercq, Bioorg. Med. Chem., 2005, 13, 6771–6776. [Crossref], [Google Scholar], [Publisher]
[28] Kato, T. Ozaki, K. Tamura, Y. Suzuki, M. Akima, N. Ohi, J. Med. Chem., 1999, 42, 3134–3146. [Crossref], [Google Scholar], [Publisher]
[29] Kato, T. Ozaki, N. Ohi, Tetrahedron Asymmetry, 1999, 10, 3963–3968. [Crossref], [Google Scholar], [Publisher]
[30] Adachi, Y. Suzuki, N. Homma, M. Fukazawa, K. Tamura, I. Nishie, O. Kuromaru, Eur. J. Pharmacol., 1999, 367, 267–273. [Crossref], [Google Scholar], [Publisher]
[31] Ottanaá, E. Mazzon, L. Dugo, F. Monforte, R. Maccari, L. Sautebin, G. De Luca, M.G. Vigorita, S. Alcaro, F. Ortuso, A.P. Caputi, S. Cuzzocrea, Eur. J. Pharmacol., 2002, 448, 71–80. [Crossref], [Google Scholar], [Publisher]
[32] Tanabe, S.H. Yamamoto, H. Okumura, G. Suzukamoc, J. Chem. Soc. Perkin Trans., 1995. [Crossref], [Google Scholar], [Publisher]
[33] K. Ashman, Int J Biochem Cell Biol., 1999, 31, 1037–1051. Crossref], [Google Scholar], [Publisher]
[34] A. Babaei, B. Kamalidehghan, M. Saleem, H.Z. Huri, F. Ahmadipour, Drug Des Devel Ther., 2016, 10, 2443–2459. [Crossref], [Google Scholar], [Publisher]
[35] A.R. Kouassi, A. Ganiyou, A. Benié, M., Koné, G. Nobel, ,K.V. Bohoussou, W.K. Coulibaly, Am. J. Pharmacol. Sci., 2021, 9, 1-29. [Crossref], [Google Scholar], [Publisher]