Malaysian Journal of Analytical Sciences, Vol 28 No 3 (2024): 711 - 723

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF NOVEL THIAZOLIDINEDIONE DERIVATIVES AS EMERGING ANTIDIABETIC AGENTS

(Sintesis, Pencirian dan Penilaian Biologi Terbitan Novel Thiazolidinedion Sebagai Agen Antidiabetik yang Baru Muncul)

Shaik Munwar¹, M K Kathiravan1^* and Ilango K^2*

¹Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu District-603203, Tamil Nadu, India

²Department of Pharmaceutical Chemistry, Tagore College of Pharmacy, Rathinamangalam, Chennai - 600 127,

Tamil Nadu, India

*Corresponding authors: ilangok67@gmail.com , kathirak@srmist.edu.in

Received: 4 January 2024; Accepted: 32 March 2024; Published: 29 June 2024

Abstract

In the present research, derivatives of thiazolidinedione were synthesized and established as potent antidiabetic activity through in vitro alpha-amylase inhibition activity and in vivo animal experimentation. A total of 15 molecules were synthesized namely, SMI-IV-2, SMI-IV-4, SMI-IV-7, SMI-IV-9, SMI-IV-11, SMI-IV-15, SMI-IV-19, SMI-IV-22, SMI-IV-23, SMI-IV-28, SMI-IV-31, SMI-IV-32, SMI-IV-34, SMI-IV-41and SMI-IV-47. Thereafter, in vitro alpha amylase activity was carried out followed by in vivo animal study performed in STZ induced animal. Metformin was used as standard for result comparison. Furthermore, various biochemical parameters were analyzed. Initially, the novel thiazolidinedione derivatives were synthesized by the reaction between thiourea and chloroacetic acid and resulted first compound as 1,3-thiazolidine-2,4-dione which was further treated with pyridine-4-carbaldehydeand resulted (5Z)-5-[(pyridin-4-yl)methylidene]-1,3-thiazolidine-2,4-dione which was further reacted with acid chloride and aromatic aldehydes and resulted the derivatives of compound (5Z)-3-[(2E)-3-phenylprop-2-enoyl]-5-[(pyridin-4-yl) methylidene]-1,3-thiazolidine-2,4-dione which was named as SMI-IV. A total of five derivatives were selected based on in vitro and in vivo results and further characterized by melting point, thin layer chromatography, IR spectroscopy, ¹HNMR, ¹³CNMR and mass spectra. In vitro alpha amylase study showed potent inhibition of alpha amylase activity by all the derivatives with dose dependent manner. Among the all derivatives, SMI-IV-4 showed IC50 value less than others (39.56%) and nearer to the standard (24.36%). In vivo animal experimentation was also revealed that derivative SMI-IV-4 significantly reduced the blood glucose level at 24 hours to 166 mg/dl when compared to the standard metformin (115 mg/dl). Overall results concluded that thiazolidinedione derivatives showed potent antidiabetic activity especially the derivatives viz. SMI-IV-4, SMI-IV-11, SMI-IV-22, SMI-IV-31, and SMI-IV-41 among them SMI-IV-4 showed more significance when compared to standard metformin.

Keywords: antidiabetic, in vitro assay, in vivo experiment, streptozotocin, spectroscopy, thiazolidinedione

Abstrak

Dalam penyelidikan ini, derivatif thiazolidinedion telah disintesis dan ditubuhkan sebagai aktiviti antidiabetik yang kuat melalui aktiviti perencatan alfa-amilase in vitro dan eksperimen haiwan in vivo. Sebanyak 15 molekul telah disintesis iaitu, SMI-IV-2, SMI-IV-4, SMI-IV-7, SMI-IV-9, SMI-IV-11, SMI-IV-15, SMI-IV-19, SMI-IV-22, SMI-IV-23, SMI-IV-28, SMI-IV-31, SMI-IV-32, SMI-IV-34, SMI-IV-41dan SMI-IV-47. Selepas itu, aktiviti amilase alfa in vitro telah dijalankan diikuti dengan kajian haiwan in vivo dilakukan dalam haiwan yang disebabkan oleh STZ. Metformin digunakan sebagai standard untuk perbandingan hasil. Tambahan pula, pelbagai parameter biokimia telah dianalisis.Pada mulanya, derivatif thiazolidinedion novel telah disintesis melalui tindak balas antara tiourea dan asid kloroasettik dan menghasilkan sebatian pertama sebagai 1,3-thiazolidine-2,4-dion yang kemudian dirawat dengan piridin-4-karbaldehid dan menghasilkan (5Z) -5- [(piridin-4-yl) metilliden]-1,3-thiazolidine-2,4-dion yang kemudiannya bertindak balas dengan asid klorida dan aldehid aromatik dan menghasilkan terbitan sebatian (5Z)-3-[(2E)-3-fenilprop-2-enoil]-5-[(piridin-4-il) metilliden]-1,3-thiazolidine-2,4-dion yang dinamakan sebagai SMI-IV. Sebanyak lima derivatif telah dipilih berdasarkan keputusan in vitro dan in vivo dan selanjutnya dicirikan oleh takat lebur, kromatografi lapisan nipis, spektroskopi IR, ¹HNMR, ¹³CNMR dan spektrum jisim. Kajian in vitro alfa amilase menunjukkan perencatan kuat aktiviti alfa amilase oleh semua derivatif dengan cara bergantung kepada dos. Di antara semua derivatif, SMI-IV-4 menunjukkan nilai IC50 kurang daripada yang lain (39.56%) dan juga lebih hampir kepada standard (24.36%). Eksperimen haiwan in vivo juga mendedahkan bahawa terbitan SMI-IV-4 dengan ketara mengurangkan paras glukosa darah pada 24 jam kepada 166 mg/dl jika dibandingkan dengan metformin standard (115 mg/dl). Keputusan keseluruhan menyimpulkan bahawa derivatif thiazolidinedion menunjukkan aktiviti antidiabetik yang kuat terutamanya derivatif iaitu SMI-IV-4, SMI-IV-11, SMI-IV-22, SMI-IV-31, dan SMI-IV-41 antaranya SMI-IV-4 menunjukkan lebih ketara jika dibandingkan dengan larutan piawai metformin.

Kata kunci: antidiabetik, ujian in vitro, eksperimen in vivo, streptozotocin, spektroskopi, thiazolidinedion

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