Sains Malaysiana 50(10)(2021): 2945-2956

http://doi.org/10.17576/jsm-2021-5010-09

Sintesis, Aktiviti Antiplasmodium dan Kesitotoksikan secara in vitro Sebatian Porfirin Logam ke atas Strain Plasmodium falciparum K1

(Synthesis, in vitro Antiplasmodial Activity and Cytotoxicity of Metalloporphyrins against Plasmodium falciparum K1 Strain)

 NUUR HAZIQAH MOHD RADZUAN¹, NUR AQILAH ZAHIRAH NORAZMI¹, AMATUL HAMIZAH ALI¹, MUNTAZ ABU BAKAR¹, HANI KARTINI AGUSTAR², MOHD RIDZUAN MOHD ABD RAZAK³ & NURUL IZZATY HASSAN¹*

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

²Department of Earth Science and Environment, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia

³Herbal Medicine Research Centre, Institute for Medical Research, National Institute of Health (NIH) Complex, Ministry of Health Malaysia, 40170 Shah Alam, Selangor Darul Ehsan, Malaysia

Received: 26 October 2020/Accepted: 14 February 2021

ABSTRAK

Jangkitan malaria adalah penyakit berjangkit serius yang disebabkan oleh parasit plasmodium dan harus dirawat sebagai perubatan kecemasan. Sehingga kini, tiada vaksin yang sudah dikomersialkan untuk mencegah malaria. Enam sebatian porfirin logam nikel(II) dan zink(II) berasaskan porfirinmeso bebas bes 5,15-difenilporfirin (2), 5,15-diheksilporfirin (3) dan 5,10,15,20-tetrafenilporfirin (4) iaitu NiDDHP, NiDPP, NiTPP, ZnDHP, ZnDPP dan ZnTPP dihasilkan melalui penyejatan Lindsey sebelum dicirikan secara spektroskopi (resonans magnet nukleus, ultra lembayung boleh nampak, spektrometri jisim) dan fizikal (takat lebur). Aktiviti antiplasmodium dan kesitotoksikan secarain vitro terhadap strain rintang-klorokuina, P. falciparum K1 dinilai dan dibandingkan dengan aktiviti antiplasmodium dadah rujukan seperti klorokuina dan artemisinin. ZnDHP, ZnTPP dan NiDPP merencat pertumbuhan parasit dengan 50% kepekatan perencatan berkesan (EC₅₀) dalam julat aktiviti antiplasmodium sederhana iaitu 21.4 sehingga 36.0 µM. Aktiviti kesitotoksikan terhadap sel mamalia Vero yang ditunjukkan oleh NiDPP, ZnDHP dan ZnTPP berada dalam julat tidak toksik iaitu 97 sehingga 587 µM. ZnDHP mempunyai nilai indeks pemilihan yang paling tinggi iaitu 27.2 µM, menunjukkan aktiviti antiplasmodium yang selektif terhadap perencatan plasmodium dan tidak toksik terhadap sel mamalia.

Kata kunci: Antiplasmodium; in vitro; kesitotoksikan; P. falciparum K1; porfirin logam

ABSTRACT

Malaria infection is a severe infectious disease caused by plasmodium parasites and should be treated as emergency medicine. Until now, no vaccine has been commercialized to prevent malaria. Six nickel(II) and zinc(II) metal porphyrin compounds based on free meso porphyrin base 5,15-diphenylporphrin (2), 5,15-dihexylporphyrin (3), and 5,10,15,20-tetraphenyl porphyrin (4), known as NiDDHP, NiDPP, NiTPP, ZnDHP, ZnDPP, and ZnTPP are produced through Lindsey condensation before being characterized by spectroscopy (nuclear magnetic resonance, ultraviolet-visible spectrophotometry, mass spectrometry) and physical (melting point). In vitro antiplasmodial and cytotoxicity activities against the P. falciparum K1 strain were assessed and compared to the antiplasmodial activity of referral drugs such as chloroquine artemisinin. ZnDHP, ZnTPP, and NiDPP recorded parasites' growth with 50% effective inhibition concentration (EC₅₀) in a range of 21.4 to 36.0 μM. Cytotoxic activities of NiDPP, ZnDHP, and ZnTPP against Vero mammalian cells were in a non-toxic range of about 97 to 587 µM. ZnDHP possessed the highest selectivity index value of 27.2 µM, indicating that the compound's antiplasmodial effect was a selective plasmodial inhibition and non-toxic to the mammalian cells.

Keywords: Antiplasmodial; cytotoxicity; in vitro; metalloporphyrin; P. falciparum K1

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*Corresponding author; email: drizz@ukm.edu.my