Sains Malaysiana 36(1): 39-44 (2007)

Safety and Toxicological Evaluation of Ferrocenium Tetrachloroantimonate

for Use as an Antimalarial Agent

(Penilaian Keselamatan dan Toksikologi Bahan Ferosenium Tetrakloroantimonat

untuk digunakan Sebagai Agen Antimalaria)

Nurhidanatasha Abu Bakar & Zainal Abidin Abu Hasan

Pusat Pengajian Biosains dan Bioteknologi

Fakulti Sains dan Teknologi, Universiti Kebangsaan Malaysia

43600 Bangi , Selangor, Malaysia

Nurul Izza Nordin & Bohari Mohamad Yamin

Pusat Pengajian Sains Kimia dan Teknologi Makanan

Fakulti Sains dan Teknologi, Universiti Kebangsaan Malaysia

43600 Bangi, Selangor, Malaysia

ABSTRACT

Ferrocene plays an important role in chemistry and industry. The structure and bonding discovered in ferrocene has led to new developments in organometallic chemistry, and the discovery of entirely new organometallic compounds. The high stability of this compound is also related to its interesting electrochemical properties that makes it effective electrochemical, reduction and combustion catalysts. Nevertheless, ferrocenyl derivatives are also capable of enhancing the activity of certain biological compounds. Indeed, recently ferrocene and its derivatives have been incorporated into antimalarial agents. Therefore, the evaluation of the possible toxic effects of ferrocene derivative called ferrocenium tetrachloroantimonate (C₁₀H₁₀FeSbCl₄ or FC) on acute and subchronic toxicity tests using different dose concentrations according to the body weight for different time interval was carried out in an in vivo model. Results showed that FC was acutely toxic with the LD₅₀ value of 194.70 mg/kg body weight (BW) with signs of toxicity associated with respiratory depression. In the 28-day acute toxicity test, the dose of 100 mg/kg BW resulted in 60 % mortality with signs of gross toxicity, adverse pharmacological effects or abnormal behaviors during the 28 days observation. While in the 90-day subchronic toxicity test at the lower dose of 10 mg/kg BW, however, showed no significant differences (p>0.05) in the mortality rates, and showed no sign of toxicity. These results indicated that FC had different toxicity levels, and mice appeared to tolerate well at the lower dose of 10 mg/kg BW.

Keywords: safety and toxicological evaluation; LD₅₀; ferrocenium tetrachloroantimonate; antimalarial agent; acute and subchronic tests

ABSTRAK

Ferosena memainkan peranan yang penting dalam bidang kimia dan industri. Penemuan struktur dan ikatannya telah merangsang perkembangan bidang kimia organologam dan penemuan kebanyakan sebatian organologam yang baru. Kestabilan struktur yang tinggi yang dipengaruhi oleh sifat elektrokimia yang menarik menjadikan ferosena sebagai pemangkin-pemangkin elektrokimia, pemangkin proses penurunan dan pemangkin proses pembakaran yang berkesan. Penggunaan sebatian terbitan ferosena juga didapati mampu meningkatkan aktiviti sebatian biologi.  Tambahan lagi, kebelakangan ini terdapat banyak percubaan menggabungkan antara ferosena dan terbitannya dengan agen antimalaria dilakukan.  Oleh itu, penilaian kesan ketoksikan terhadap sebatian terbitan ferosena yang dinamakan ferosenium tetrakloroantimonat (C₁₀H₁₀FeSbCl₄ atau FC) telah dilakukan secara in vivo melibatkan ujian ketoksikan akut dan subkronik menggunakan dos-dos yang berbeza berdasarkan perbezaan berat tubuh dan jangka masa perlakuan. Keputusan menunjukkan bahawa ketoksikan akut telah dikesan dengan FC dengan nilai LD₅₀ = 194.70 mg/kg berat tubuh (BT) dengan tanda-tanda ketoksikan yang berkaitan dengan pernafasan. Ujian ketoksikan akut 28 hari dengan perlakuan dos 100 mg/kg BT juga menyebabkan 60 % kematian dengan tanda-tanda ketoksikan yang ketara, kesan sampingan farmakologi atau kelakuan yang abnormal sepanjang tempoh pemerhatian selama 28 hari. Manakala dalam ujian ketoksikan subkronik 90 hari dengan dos 10 mg/kg BT bagaimanapun tidak menunjukkan kadar kematian yang signifikan (p>0.05) dan tiada tanda ketoksikan pada mencit dikesan. Hasil-hasil kajian ini menunjukkan bahawa FC mempunyai tahap ketoksikan yang berbeza-beza dan mencit bertoleransi dengan baik terhadap dos rendah 10 mg/kg BT .

Kata kunci: penilaian keselamatan dan toksikologi; LD₅₀, ferosenium tetrakloroantimonat; agen antimalaria; ujian akut dan ujian subkronik

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