Sains Malaysiana 54(3)(2025): 869-879

http://doi.org/10.17576/jsm-2025-5403-19

Thiocolchicoside Ameliorated Glycation via Lysine Blockade and Carbonyl Entrapment

(Thiocolchicoside Diperbaharui Glisasi melalui Sekatan Lisin dan Perangkap Karbonil)

NAJEEB KHATIAN¹, TALHA BIN FAYYAZ¹, HAMMAD AHMED¹, UZAIR NISAR¹, MOHAMMAD ABID³, SHUMAILA USMAN², SYED ABID ALI³ & GHULAM ABBAS^1,*

¹Department of Pharmacology, Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan
²Department of Molecular Medicine, Ziauddin University, Karachi, Pakistan
³H.E.J. Research Institute of Chemistry, International Center for Chemical & Biological Sciences, University of Karachi, Karachi, Pakistan

Received: 30 March 2024/Accepted: 13 December 2024

Abstract

The phenomenon of glycation leads to formation of AGE, which plays central role in various health hazards and accelerates the aging process. The re-purposing approach provide rapid means to introducing potential leads to drug discovery program. Keeping this into account, the present study investigates thiocolchicoside, for its capacity to be repurposed as anti-glycation agent.  To assess the anti-glycation potential, thiocolchicoside was selected on the basis SAR, it is a muscle relaxant which is synthetic derivative of colchicoside, thiocolchicoside at 0.5, 1 and 2 mM were used and tested on various assays such as AGE inhibition assay (intrinsic fluorescence), fructosamine adduct formation (NBT assay) and availability of free lysine by using TNBSA followed by Lysine blockade assay (OPA and molecular docking study). The structural changes in the BSA protein was determined by using the thioflavin-T and Congo red assays. Finally, the carbonyl entrapment assay also performed to confirm the mechanism of the anti-glycation action. Thiocolchicoside significantly reduced the AGEs production in BSA-fructose model with an IC₅₀ value of 0.25 mM. The fructosamine adducts were found to be reduced along with enhanced availability of free lysine. Furthermore, it exhibited lysine blockade activity which was also validated by computational study. Thiocolchicoside also prevented the alteration in glycation mediated BSA conformation. Furthermore, it was also found to entrap carbonyl moieties. Thiocolchicoside has a showed the significant anti-glycation potential, which can be attributed to its ability to block lysine residue and entrap carbonyl compounds. Hence, this clinically used muscle relaxant present itself as a potential drug to be repurposed as anti-glycation agent.  

Keywords: BSA; glycation; HPLC; repurposing; thiocolchicoside

Abstract

Fenomena glikasi membawa kepada pembentukan AGE, yang memainkan peranan utama dalam pelbagai bahaya kesihatan dan mempercepatkan proses penuaan. Pendekatan guna semula menyediakan cara pantas untuk memperkenalkan potensi petunjuk kepada program penemuan dadah. Dengan mengambil kira perkara ini, penyelidikan ini mengkaji thiocolchicoside untuk kapasitinya untuk digunakan semula sebagai agen anti-glikasi. Untuk menilai potensi anti-glikasi, thiocolchicoside telah dipilih berdasarkan SAR, ia adalah relaksan otot yang merupakan terbitan sintetik colchicoside, thiocolchicoside pada 0.5, 1 dan 2 mM telah digunakan dan diuji pada pelbagai ujian seperti asai perencatan AGE (intrinsik pendarflour) dan pembentukan fruktosamin secara bebas oleh aduk. TNBSA diikuti dengan asai sekatan lisin (OPA dan kajian dok molekul). Perubahan struktur dalam protein BSA ditentukan dengan menggunakan thioflavin-T dan ujian merah Congo. Akhir sekali, ujian perangkap karbonil juga dilakukan untuk mengesahkan mekanisme tindakan anti-glikasi. Thiocolchicoside telah mengurangkan pengeluaran AGEs dengan ketara dalam model BSA-fruktosa dengan nilai IC₅₀ sebanyak 0.25 mM. Tambahan fruktosamin didapati berkurangan bersama-sama dengan peningkatan ketersediaan lisin bebas. Tambahan pula, ia menunjukkan aktiviti sekatan lisin yang juga disahkan oleh kajian pengiraan. Thiocolchicoside juga menghalang perubahan dalam konformasi BSA pengantara glikasi. Tambahan pula, ia juga didapati memerangkap bahagian karbonil. Thiocolchicoside mempunyai potensi anti-glikasi yang ketara yang boleh dikaitkan dengan keupayaannya untuk menyekat sisa lisin dan memerangkap sebatian karbonil. Oleh itu, pelemas otot yang digunakan secara klinikal ini menunjukkan dirinya sebagai ubat yang berpotensi untuk digunakan semula sebagai agen anti-glikasi.

Kata kunci: BSA; glikasi; guna semula; HPLC; thiocolchicoside

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*Corresponding author; email: ghulam.abbas@hotmail.com