Malaysian Journal of Analytical Sciences Vol 25 No 6 (2021): 1020 - 1031

 

 

 

 

CYTOTOXICITY EFFECT OF NATURAL AND SYNTHETIC GIRINIMBINES AND THEIR DERIVATIVES AGAINST HUMAN LUNG CANCER CELL LINES A549

 

(Kesan Sitotoksik Girinimbin Semula Jadi dan Sintetik dan Terbitannya Terhadap Sel Garis Kanser Paru-Paru Manusia A549)

 

Fatin Nurul Atiqah Osman¹, Siti Mariam Mohd Nor¹*, Mohd Azlan Nafiah²

 

¹Department of Chemistry, Faculty of Science,

Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

²Department of Chemistry, Faculty of Science and Mathematics,

Universiti Pendidikan Sultan Idris, 35900 Tanjung Malim, Perak, Malaysia

 

*Corresponding author:  smariam@upm.edu.my

 

 

Received:  8 September 2021; Accepted: 18 November 2021; Published:  27 December 2021

 

 

Abstract

The present study was designed to evaluate the anticancer properties of girinimbine and its derivatives. Two different routes for the synthesis of girinimbine involving a two-step reaction or a one-pot reaction were studied. Girinimbine was synthesised through metal-catalysed heterocoupling, indole ring closure, ether formation, and Claisen cyclisation. Girinimbine derivatives were prepared by the semi-synthesis of isolated girinimbine from Murraya koenigii through alkylation or acylation reactions. Natural and synthetic girinimbines, five derivatives of N-substituted girinimbine, and three intermediates from the synthesis of girinimbine were evaluated for cytotoxicity activity against human lung cancer (A549) and normal lung (MRC-5) cell lines. The structures of all the synthesised compounds were confirmed by spectroscopic analysis and comparison with published data. The cytotoxicity assay showed that the natural girinimbine and nitrobiphenyl intermediate exhibited high toxicity (IC₅₀ 6.2 and 17.0 μg/mL, respectively), whereas other compounds displayed moderate toxicity activity (IC₅₀ 24.0–40.6 μg/mL) on A549 cells. All of the compounds demonstrated selectivity to A549 cancer cell lines with the SI values ranging from 2.70 to 4.68 (SI > 2), except for two N-alkylated girinimbines with the SI values of 0.93 and 1.70.

 

Keywords:  girinimbine, derivative, N-alkylated, N-acylated, A549

 

Abstrak

Kajian ini telah dibentuk untuk menilai sifat antikanser girinimbin dan terbitannya. Dua laluan berbeza untuk mensintesis girinimbin melibatkan tindak balas dua-langkah atau tindak balas satu-bekas telah dikaji. Sintesis girinimbin telah dicapai melalui penggandingan hetero bermangkin logam, penutupan gelang indol, pembentukan eter dan pensiklikan Claisen. Terbitan girinimbin telah disediakan melalui sintesis-semi girinimbin terpencil daripada Murraya koenigii melalui tindak balas pengalkilan atau pengasilan. Girinimbin semula jadi dan sintetik, lima terbitan girinimbin tertukar ganti-N dan tiga bahan perantara daripada kerja sintesis telah dinilai untuk aktiviti sitotoksik terhadap sel garis kanser paru-paru manusia (A459) dan paru-paru normal (MRC-5). Kesemua struktur sebatian yang disintesis telah disahkan melalui analisis spektroskopik dan perbandingan dengan data yang telah diterbitkan. Assai kesitotoksikan menunjukkan girinimbin semula jadi dan bahan perantara bifenilnitro telah memaparkan ketoksikan tinggi (IC₅₀ 6.2 and 17.0 μg/mL) manakala sebatian yang lain menunjukkan aktiviti ketoksikan sederhana (IC₅₀ 24.0-40.6 μg/mL) ke atas sel A549. Kesemua sebatian menunjukkan kepilihan kepada sel garis kanser A459 dengan nilai SI dalam julat daripada 2.70-4.68 (SI > 2) kecuali dua girinimbin teralkil-N dengan nilai SI 0.93 dan 1.70.

 

Kata kunci:  girinimbin, terbitan, teralkil-N, terasil-N, A549

 

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