Empat Senyawa Analog Pirazinamida: Sintesis, Bioaktivitas terhadap Mycobacterium tuberculosis H37Rv, dan Studi In Silico

Zulqurnain, Muhammad (2021) Empat Senyawa Analog Pirazinamida: Sintesis, Bioaktivitas terhadap Mycobacterium tuberculosis H37Rv, dan Studi In Silico. Masters thesis, Institut Teknologi Sepuluh Nopember.

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Abstract

Tuberkulosis merupakan penyakit infeksi menular yang diakibatkan oleh bakteri Mycobacterium tuberculosis, dapat menyerang khususnya organ paru-paru. Jumlah penderita tuberkulosis mencapai 10 juta jiwa pada tahun 2018, dan 8% diantaranya berada di Indonesia. Jumlah kasus TB di Indonesia mengalami penurunan pada tahun 2000 hingga tahun 2018, tetapi mengalami kenaikan kasus TB baru dan kambuh pada periode tersebut. Faktor penting penyebab kenaikan kasus TB kambuh adalah adanya resisten terhadap obat tuberkulosis yang disebut multi drug resistance-TB (MDR-TB), yang muncul disebabkan pasien tidak konsisten dalam menjalani pengobatan selama enam bulan. Pirazinamida (1a) berperan penting dalam memperpendek pengobatan dan penghambatan bakteri M. tuberculosis yang kuat dibandingkan dengan obat tuberkulosis lain. Sehubungan dengan kelebihan tersebut, maka perlu dikembangkan senyawa-senyawa analog pirazinamida (1a) dengan bioaktivitas yang lebih baik. Penelitian yang telah dilakukan berhasil mensintesis empat senyawa analog pirazinamida (1a) baru berupa: N-(4-etilfenil)pirazina-2-karboksamida (7a), N-sikloheptilpirazina-2-karboksamida (7b), N-oktilpirazina-2-karboksamida (7c), dan N-(4-klorobenzil)pirazina-2-karboksamida (7d) dengan metode esterifikasi Yamaguchi. Uji bioaktivitas terhadap Mycobacterium tuberculosis H37Rv mendapatkan bahwa senyawa 7d mempunyai bioaktivitas yang lebih baik (mempunyai MIC<6,25 μg/mL) dari senyawa 7a-c (mempunyai MIC >25 μg/mL) maupun pirazinamida (1a) dengan MIC 12,5 μg/mL. Hasil uji tersebut selaras dengan hasil studi in silico yang mendapat bahwa binding energy senyawa 7a-d tidak melanggar aturan Lipinski yang biasa dimanfaatkan sebagai parameter umum dalam pengembangan obat. ==================================================================================================== Tuberculosis is a contagious infectious disease caused by the bacteria Mycobacterium tuberculosis, which can attack especially the lungs. The number of tuberculosis sufferers reached 10 million in 2018, and 8% of them are in Indonesia. The number of TB cases in Indonesia decreased from 2000 to 2018, but experienced an increase in new and recurrent TB cases during the period. An important factor causing the increase in TB cases of recurrence is the presence of resistance to a tuberculosis drug called multi drug resistance-TB (MDR-TB), which arises because patients are inconsistent in undergoing treatment for six months. Pyrazinamide (1a) plays an important role in shortening the treatment and inhibition of the strong M. tuberculosis bacteria compared to other tuberculosis drug. In connection with these advantages, it is necessary to develop pyrazinamide (1a) analog compounds with better bioactivity. The research that has been carried out has succeeded in synthesizing four new pyrazinamide (1a) analogues in the form of: N-(4-ethylphenyl)pyrazine-2-carboxamide (7a), N-cycloheptylpyrazine-2-carboxamide (7b), N-octylpyrazine-2-carboxamide (7c), and N-(4-chlorobenzyl)pyrazine-2-carboxamide (7d) by the Yamaguchi esterification methode. Bioactivity test against Mycobacterium tuberculosis H37Rv found that 7d compound has better bioactivity (has MIC <6,25 μg/mL) than 7a-c compound (has MIC >25 μg/mL) and pyrazinamide (1a) with MIC 12,5 μg/mL. The test results are in line with the results of the in silico study which found that the binding energy of 7d compound is better than 7a-c and pyrazinamide (1a) compounds. Furthermore, 7a-d compounds do not violate Lipinski`s rules which are commonly used as general parameters in drug development.

Item Type: Thesis (Masters)
Uncontrolled Keywords: tuberculosis, pyrazinamide analogue, Yamaguchi esterification method, in vitro, in silico, tuberkulosis, analog pirazinamida, metode esterifikasi Yamaguchi, in vitro, in silico.
Subjects: Q Science > QD Chemistry > QD251.2 Chemistry, Organic. Biochemistry
Q Science > QD Chemistry > QD471 Chemical compounds - Structure and formulas
Divisions: Faculty of Science and Data Analytics (SCIENTICS) > Chemistry > 47101-(S2) Master Thesis
Depositing User: Muhammad Zulqurnain
Date Deposited: 10 Mar 2021 01:18
Last Modified: 10 Mar 2021 01:18
URI: https://repository.its.ac.id/id/eprint/83993

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