Design, Synthesis, and Molecular Docking Studies of a Conjugated Thiadiazole–Thiourea Scaffold as Antituberculosis Agents
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- Tatar Esra
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University
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- Karakuş Sevgi
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University
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- Küçükgüzel Şükriye Güniz
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University
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- Öktem Okullu Sinem
- Department of Medical Microbiology, School of Medicine, Acıbadem University
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- Ünübol Nihan
- Department of Medical Microbiology, School of Medicine, Acıbadem University
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- Kocagöz Tanıl
- Department of Medical Microbiology, School of Medicine, Acıbadem University
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- De Clercq Erik
- Rega Institute for Medical Research
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- Andrei Graciela
- Rega Institute for Medical Research
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- Snoeck Robert
- Rega Institute for Medical Research
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- Pannecouque Christophe
- Rega Institute for Medical Research
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- Kalaycı Sadık
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University
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- Şahin Fikrettin
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University
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- Sriram Dharmarajan
- Medicinal Chemistry and Drug Discovery Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science-Pilani
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- Yogeeswari Perumal
- Medicinal Chemistry and Drug Discovery Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science-Pilani
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- Küçükgüzel İlkay
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University
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Abstract
In view of the emergence and frequency of multidrug-resistant and extensively drug-resistant tuberculosis and consequences of acquired resistance to clinically used drugs, we undertook the design and synthesis of novel prototypes that possess the advantage of the two pharmacophores of thiourea and 1,3,4-thiadiazole in a single molecular backbone. Three compounds from our series were distinguished from the others by their promising activity profiles against Mycobacterium tuberculosis strain H37Rv. Compounds 11 and 19 were the most active representatives with minimum inhibitory concentration (MIC) values of 10.96 and 11.48 µM, respectively. Compound 15 was shown to inhibit M. tuberculosis strain H37Rv with an MIC value of 17.81 µM. Cytotoxicity results in the Vero cell line showed that these three derivatives had selectivity indices between 1.8 and 8.7. In order to rationalize the biological results of our compounds, molecular docking studies with the enoyl acyl carrier protein reductase (InhA) of M. tuberculosis were performed and compounds 11, 15, and 19 were found to have good docking scores in the range of −7.12 to −7.83 kcal/mol.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 39 (4), 502-515, 2016
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204631776000
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- NII Article ID
- 130005141685
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 027220761
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- PubMed
- 27040623
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed