Syarifudin, Muhammad Rajwasabiq (2025) Sintesis N’-((Indol-5-il)metilena)isonikotinohidrazida Dan N’-((Indol-6-il)metilena)isonikotinohidrazida Serta Uji Bioaktivitasnya Terhadap Mycobacterium Tuberculosis H37Rv. Other thesis, Institut Teknologi Sepuluh Nopember.
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Abstract
Berdasarkan laporan dari Kementerian Kesehatan Republik Indonesia (2023), Indonesia menempati urutan kedua tertinggi di dunia dalam jumlah kasus TBC, dengan estimasi 808.000 kasus TBC sensitif obat, serta sekitar 121 kasus baru dan 15 kematian akibat TBC setiap jam. Penanganan TBC umumnya mengandalkan regimen obat lini pertama seperti isoniazid (1) dan rifampisin (2). Namun, ketidakpatuhan, penggunaan obat yang tidak tepat, serta keterlambatan diagnosis telah menjadi faktor utama dalam munculnya kasus Multi Drug-Resistant Tuberculosis (MDR-TB) hingga Extensively Drug Resistant (XDR) TB yang Resistensi terhadap obat tuberkulosis. 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’-((indol-5-il)metilena)isonikotinohidrazida (8a) dan N’-((indol-6-il)metilena)isonikotinohidrazida (8b). Sintesis senyawa hidrazon 8a melibatkan reaksi isoniazid (1) dengan Indol-5-karboksaldehida (9a), sedangkan sintesis senyawa hidrazon 8b melibatkan reaksi isoniazid (1) dengan Indol-6-karboksaldehida (9b). Sintesis dilakukan dalam pelarut etanol pada kondisi refluks dengan katalis HCl dan diperoleh senyawa N’-((indol-5-il)metilena)isonikotinohidrazida (8a) dengan rendemen 89% dan senyawa N’-((indol-6-il)metilena)isonikotinohidrazida (8b) dengan rendemen 71%. 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 μg/mL; sehingga MIC senyawa 8a-b sebesar <6,25 μg/mL. Isoniazid (1) sebagai senyawa pembanding mempunyai MIC sebesar 0,0625 μg/mL, sedangkan pirazinamida (12) menurut literatur mempunyai MIC sebesar 50 μg/mL.
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Based on a report from the Ministry of Health of the Republic of Indonesia (2023), Indonesia ranks second highest in the world in the number of TB cases, with an estimated 808,000 cases of drug-sensitive TB, as well as approximately 121 new cases and 15 deaths from TB every hour. TB treatment generally relies on first-line drug regimens such as isoniazid (1) and rifampicin (2). However, non-compliance, inappropriate drug use, and delayed diagnosis have become major factors in the emergence of Multi Drug-Resistant Tuberculosis (MDR-TB) to Extensively Drug Resistant (XDR) TB cases. Drug-resistant M. tuberculosis poses a major challenge to global TB eradication efforts, necessitating the development of new anti-TB compounds. Isoniazid (1) is the main drug used for the treatment of tuberculosis because it is able to inhibit the growth of M. tuberculosis H37Rv with MIC ranging from 0.03-0.1 μg/mL. Isoniazid derivatives are then utilized as lead compounds in the development of new TB drugs. The research conducted has successfully obtained isoniazid-derived hydrazone compounds in the form of N’-((indol-5-yl)methylene)isonicotinohydrazide (8a) and N’-((indol-6-yl)methylene)isonicotinohydrazide (8b). The synthesis of hydrazone compound 8a involved the reaction of isoniazid (1) with Indol-5-carboxaldehyde (9a), while the synthesis of hydrazone compound 8b involved the reaction of isoniazid (1) with Indol-6-carboxaldehyde (9b). The synthesis was carried out in ethanol solvent at reflux condition with catalyst and obtained N’-((indol-5-yl)methylene)isonicotinohydrazide (8a) compound with 89% yield and N’-((indol-6-yl)methylene)isonicotinohydrazide (8b) compound with 71% yield. Purity tests of hydrazone compounds 8a-b were performed by thin-layer chromatography and melting point; structural identification of hydrazone compounds 8a-b was performed by NMR spectrometer (1H and 13C), FTIR spectrophotometer, and high-resolution mass spectrometer. Bioactivity tests of compounds 8a-b showed that M. tuberculosis H37Rv did not grow at concentrations of 25; 12.5; and 6.25 μg/mL; so that the MIC of compound 8a-b is <6.25 µg/mL. Isoniazid (1) as a comparison 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: | Hidrazon, Isoniazid, N’-((indol-5-il)metilena)isonikotinohidrazida, N’-((indol-6-il)metilena)isonikotinohidrazida, Hydrazone, N’-((indol-5-yl)methylene)isonicotinohydrazide, N’-((indol-6-yl)methylene)isonicotinohydrazide |
| Subjects: | Q Science > QD Chemistry > QD471 Chemical compounds - Structure and formulas |
| Divisions: | Faculty of Science and Data Analytics (SCIENTICS) > Chemistry > 47201-(S1) Undergraduate Thesis |
| Depositing User: | Muhammad Rajwasabiq Syarifudin |
| Date Deposited: | 12 Nov 2025 08:27 |
| Last Modified: | 12 Nov 2025 08:27 |
| URI: | http://repository.its.ac.id/id/eprint/128521 |
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