Sintesis dan Bioaktivitas Hidrazon terhadap Mycobacterium tuberculosis H37Rv

Fauzi, Ahmad Saharuddin (2025) Sintesis dan Bioaktivitas Hidrazon terhadap Mycobacterium tuberculosis H37Rv. Other thesis, Institut Teknologi Sepuluh Nopember.

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Abstract

Studi yang dilakukan di Amerika Serikat dan Kanada mendapatkan bahwa sebanyak 158 dari 4.490 responden yang kontak erat dengan pasien tuberkulosis paru aktif terdiagnosis tertular penyakit tuberkulosis pada tahun 2006-2009. Pengobatan terhadap infeksi M. tuberculosis dilakukan dengan obat-obat tuberkulosis (TB). Resistensi terhadap obat tuberkulosis terdapat dalam bentuk multidrug-resistant (MDR) TB hingga extensivelydrug -resistant (XDR) TB. M. tuberculosis yang resisten terhadap obat-obat tuberkulosis menjadi tantangan besar dalam upaya pemberantasan TB secara global, sehingga diperlukan pengembangan senyawa-senyawa anti-TB baru. Isoniazid (1) merupakan obat utama yang digunakan untuk pengobatan tuberkulosis karena mampu menghambat pertumbuhan M. tuberculosis H37Rv dengan MIC berkisar antara 0,03-0,1 μg/mL. Turunan-turunan isoniazid selanjutnya dimanfaatkan sebagai lead compounds dalam pengembangan obat TB baru. Penelitian yang dilakukan telah berhasil mendapatkan senyawa-senyawa hidrazon turunan isoniazid berupa N’-(2-bromobenziliden)isonikotinohidrazida (8a) dan N’-(2-fluoro-benziliden)isonikotinohidrazida (8b). Sintesis senyawa hidrazon 8a melibatkan reaksi isoniazid (1) dengan 2-bromobenzaldehida (9a), sedangkan sintesis senyawa hidrazon 8b melibatkan reaksi isoniazid (1) dengan 2-fluorobenzaldehida (9b). Sintesis dilakukan dalam pelarut etanol pada kondisi refluks tanpa katalis dan diperoleh senyawa N’-(2-bromo-benziliden)isonikotinohidrazida (8a) dengan rendemen 76% dan senyawa N’-(2-fluoro-benziliden)isonikotinohidrazida (8b) dengan rendemen 89%. Uji kemurnian senyawa hidrazon 8a-b dilakukan dengan kromatografi lapis tipis dan titik leleh; identifikasi struktur senyawa hidrazon 8a-b dilakukan dengan spektrometer NMR (1H dan 13C), spektrofotometer FTIR, dan spektrometer massa resolusi tinggi. Uji bioaktivitas senyawa 8a-b menunjukkan bahwa M. tuberculosis H37Rv tidak tumbuh pada konsentrasi 25; 12,5; dan 6,25 g/mL. Isoniazid (1) sebagai senyawa pembanding mempunyai MIC sebesar 0,0625 μg/mL, sedangkan pirazinamida (25) menurut literatur mempunyai MIC sebesar 50 μg/mL.
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A study conducted in the United States and Canada found that 158 out of 4.490 respondents who had close contact with patients with active pulmonary tuberculosis were diagnosed with tuberculosis infection during the years 2006-2009. The treatment of Mycobacterium tuberculosis infection is carried out using tuberculosis (TB) drugs. Drug resistance in tuberculosis is categorized into multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB. Drug-resistant M. tuberculosis poses a significant challenge to global TB eradication efforts, necessitating the development of new anti-TB compounds. Isoniazid (1) is a primary drug used in TB treatment due to its ability to inhibit the growth of M. tuberculosis H37Rv with a minimum inhibitory concentration (MIC) ranging from 0.03 to 0.1 μg/mL. Derivatives of isoniazid have been further utilized as lead compounds in the development of new TB drugs. Research has successfully synthesized hydrazone derivatives of isoniazid, namely N’-(2-bromobenzylidene)isonicotinohydrazide (8a) and N’-(2-fluorobenzylidene)-isonicotinohydrazide (8b). The synthesis of hydrazone 8a involved the reaction of isoniazid (1) with 2-bromobenzaldehyde (9a), while hydrazone 8b was synthesized through the reaction of isoniazid (1) with 2-fluorobenzaldehyde (9b). Both syntheses were carried out in ethanol solvent under reflux conditions without a catalyst, yielding N’-(2-bromobenzylidene)-isonicotinohydrazide (8a) with a yield of 76% and N’-(2-fluorobenzylidene)-isonicotinohydrazide (8b) with a yield of 89%. The purity of hydrazone compounds 8a-b was analyzed using thin-layer chromatography (TLC) and melting point determination, while structural identification was performed using NMR spectroscopy (¹H and ¹³C), FTIR spectrophotometry, and high-resolution mass spectrometry (HRMS). Bioactivity tests on compounds 8a-b demonstrated that M. tuberculosis H37Rv did not grow at concentrations of 25, 12.5, and 6.25 μg/mL. In comparison, isoniazid (1) as a reference compound has an MIC of 0.0625 μg/mL, while pyrazinamide (25), according to the literature, has an MIC of 50 μg/mL.

Item Type:	Thesis (Other)
Uncontrolled Keywords:	2-bromobenzaldehid, 2-fluorobenzaldehid, Hidrazon, Isoniazid
Subjects:	Q Science > QD Chemistry > QD251.2 Chemistry, Organic. Biochemistry
Divisions:	Faculty of Science and Data Analytics (SCIENTICS) > Chemistry > 47201-(S1) Undergraduate Thesis
Depositing User:	Ahmad Saharuddin Fauzi
Date Deposited:	06 Feb 2025 08:55
Last Modified:	06 Feb 2025 08:55
URI:	http://repository.its.ac.id/id/eprint/118496

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