Sains Malaysiana 52(11)(2023): 3325-3342

http://doi.org/10.17576/jsm-2023-5211-22

Elucidating the Binding Affinity of Meso Porphyrin Derivatives with Bcl-2 through Synthesis and Molecular Docking Analysis

(Elusidasi Kekuatan Ikatan Terbitan Meso Porfirin melalui Analisis Sintesis dan Pendokan Molekul)

YASOTHAA RAMAIYAH^1,2, MOHD BAKRI BAKAR³ & MUNTAZ ABU BAKAR^1,*

¹Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

 ²National Pharmaceutical Regulatory Agency, Ministry of Health Malaysia,

46200 Petaling Jaya, Selangor, Malaysia

³Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia,

 81310 UTM Johor Bahru, Johor, Malaysia

Diserahkan: 14 September 2023/Diterima: 4 Disember 2023

Abstract

Reversing multi-drug resistance in a clinical setting remains a formidable issue to date. Porphyrin has high efficiency to conjugate with chemotherapy drugs and effectively deliver within the nucleus of cancer cells which helps in lowering side effect to normal cells. As compared to naturally occurring beta-substituted porphyrins, synthetic meso-substituted porphyrins have numerous benefits. An extensive variety of substituents have been developed with porphyrins. There are eight new porphyrin derivatives synthesised in this research compounds 14-21 which differ from one size to another using Sonogashira and Suzuki coupling techniques. Sonogashira coupling method undergoes a reaction between alkyne terminal sp hybridized carbon and vinyl halide’s sp² carbon in the presence of a Palladium catalyst. Furthermore, Suzuki coupling method has been an effective method in conjugation of aryl halides and borylated porphyrins. The synthesized new compounds were characterized by ultra-violet spectroscopy (UV-Vis), high resolution mass spectrometer (HRMS) and nuclear magnetic resonance (NMR) to confirm successful formation of all new compounds. The docking analysis was performed for compound 14-21. Compounds 16 and 18 showed the greater binding mode at the Bcl-2 protein pocket regards free or metal substituted porphyrin with longer linker chain and less bulky compared to compounds 17 and 19. This study could discover the structure of porphyrin that affects accumulation in cancer cells that potentially transmissible to target tumour.

Keywords: Bcl-2 protein; molecular docking; porphyrin; Sonogashira coupling; Suzuki coupling

Abstrak

Pemulihan rintangan pelbagai ubat dalam persekitaran klinikal kekal sebagai isu yang sangat kritikal setakat ini. Porfirin mempunyai kecekapan tinggi untuk bergabung dengan ubat kemoterapi dan berkesan menyampaikan ubat dalam nukleus sel kanser dan ini membantu mengurangkan kesan sampingan terhadap sel normal. Terbitan porfirin boleh diaplikasikan dalam pelbagai bidang bergantung kepada penukarganti yang diperkenalkan kepada porfirin. Berbanding dengan beta-porfirin yang wujud secara semula jadi, porfirin yang ditukarganti pada kedudukan meso secara sintetik mempunyai banyak faedah. Pelbagai jenis penukarganti porfirin telah dibangunkan. Terdapat lapan sebatian porfirin baru iaitu sebatian 14-21 yang disintesis dalam penyelidikan ini menggunakan tindak balas penggandingan Sonogashira dan Suzuki. Penggandingan Sonogashira adalah tindak balas antara karbon terhibrid terminal alkuna sp dan karbon vinil halida sp². Manakala, tindak balas Suzuki adalah teknik konjugasi aril halida dan porfirin terborilasi. Sebatian baharu yang disintesis telah dicirikan dengan menggunakan kaedah ultra-lembayung boleh nampak (ULBN), spektrometer jisim resolusi tinggi dan resonans magnet nuklear (RMN). Analisis dok telah dilakukan bagi sebatian 14-21. Sebatian 16 dan 18 menunjukkan mod pengikatan yang lebih besar pada poket protein Bcl-2 iaitu sama ada bebas atau porfirin yang digantikan logam dengan rantai penghubung yang lebih panjang dan kurang besar berbanding kompaun 17 dan 19. Kajian ini menunjukkan bagaimana struktur porfirin mempengaruhi penumpukan dalam sel kanser yang berpotensi untuk dihantar kepada tumor sasaran.

Kata kunci: Dok molekul; penggandingan Sonogashira; penggandingan Suzuki; porfirin; Protein Bcl-2

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*Pengarang untuk surat-menyurat; email: muntaz@ukm.edu.my