Senyawa-Senyawa Sinamamida: Pengembangan Metoda Sintesis, Bioaktivitas Terhadap Mycobacterium Tuberculosis H37Rv Dan Studi In Silico

Rahayu, Reni (2021) Senyawa-Senyawa Sinamamida: Pengembangan Metoda Sintesis, Bioaktivitas Terhadap Mycobacterium Tuberculosis H37Rv Dan Studi In Silico. Masters thesis, Institut Teknologi Sepuluh Nopember.

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Abstract

Tuberkulosis (TB) merupakan penyakit infeksi kronis yang disebabkan Mycobakterium tuberculosis (Mtb) yang menyerang organ terutama paru-paru. Terapi penyakit tuberkulosis terkendala dengan adanya resistensi terhadap obat anti tuberkulosis (OAT) yang ada dan disebut sebagai Multi Drug Resistance Tuberculosis (MDR-TB), Extensively Drug Resistant Tuberculosis (XDR-TB), dan Totally Drug Resistant Tuberculosis (TDR-TB). Pengembangan OAT baru akibatnya sangat mendesak. Turunan asam sinamat berupa sinamamida diketahui menunjukkan aktivitias terhadap M. tuberculosis H37Rv sehingga pada penelitian ini dimanfaatkan sebagai lead compound dalam pengembangan senyawa-senyawa anti-tuberkulosis. Sintesis senyawa-senyawa sinamamida pada umumnya dilakukan dengan melibatkan tionil klorida yang termasuk Chemical Weapons Conventions, dan Bahan Kimia Daftar-3 di Undang-undang Republik Indonesia Nomor 9 tahun 2008 tentang penggunaan bahan kimia dan larangan penggunaan bahan kimia sebagai senjata kimia. Penelitian yang dilakukan berhasil mendapatkan metoda baru sintesis sinamamida yang tidak melibatkan tionil klorida; dan diterapkan untuk sintesis N-(4-klorobenzil)sinamamida (23a), N-oktilsinamamida (23b), N-sikloheksilsinamamida (23c), dan N-sikloheptilsinamamida (23d) dengan rendemen 60-92%. Uji in vitro mendapatkan bahwa senyawa 23a-d dan pirazinamida (3) sebagai senyawa pembanding menunjukkan bioaktivitas terhadap M. tuberculosis H37Rv dengan MIC >25 g/mL. Hasil in silico senyawa 23a-d dan pirazinamida (3) menggunakan PDB 4TZK mendapatkan bahwa senyawa 23a memiliki binding energy yang lebih baik dari pada senyawa 23b-d maupun pirazinamida (3) dan asam sinamat (5); dan senyawa 23a-d memenuhi aturan Lipinski sebagai obat oral yang baik.

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Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) which attacks the lungs. Tuberculosis therapy is constrained by resistance to existing anti-tuberculosis drugs (OAT) known as Multi-Drug-Resistant Tuberculosis (MDR-TB), Extensively Drug-Resistant Tuberculosis (XDR-TB), and Totally Drug-Resistant Tuberculosis (TDR-TB) so the development of new drugs is very important. Cinnamamide (derivative from cinnamic acid) is known to show activity against M. tuberculosis H37Rv so that it can be used as a lead compound in the development of anti-tuberculosis compounds. Synthesis of cinnamamide compounds is generally carried out by involving thionyl chloride which is included in Chemical Weapons Conventions and is listed as chemical list-3 in the Law of the Republic of Indonesia Number 9 of 2008 concerning the use of chemicals and the prohibition of the use of chemicals as chemical weapons. The research carried out succeeded in obtaining a new method of synamamide synthesis that did not involve thionyl chloride; and applied to the synthesis of N-(4-chlorobenzyl)cinamamide (23a), N-octylcinamamide (23b), N-cyclohexylcinamamide (23c), and N-cycloheptilcinamamide (23d) with a yield of 60-92%. The in vitro test conducted found that compounds 23a-d and pyrazinamide (3) as comparison compounds showed bioactivity against M. tuberculosis H37Rv with MIC >25 g/mL. The results of in silico for compounds 23a-d and pyrazinamide (3) using PDB 4TZK found that compound 23a had better binding energy than compounds 23b-d and pyrazinamide (3) and cinnamic acid (5); and compounds 23a-d meet Lipinski's rule as a good oral drug.

Item Type:	Thesis (Masters)
Uncontrolled Keywords:	Tuberkulosis, sinamamida, sintesis, in vitro, in silico Tuberculosis, cinnamamide, synthesis, in vitro, in silico
Subjects:	Q Science > QD Chemistry Q Science > QD Chemistry > QD251.2 Chemistry, Organic. Biochemistry
Divisions:	Faculty of Natural Science > Chemistry > 47101-(S2) Master Thesis
Depositing User:	Reni Rahayu
Date Deposited:	27 Aug 2021 03:13
Last Modified:	27 Aug 2021 03:13
URI:	http://repository.its.ac.id/id/eprint/89839

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