In vitro bactericidal activities of two novel dihydropyridine derivatives against Mycobacterium tuberculosis
Introduction: Introducing new and effective antitubercular agents is important in tuberculosis control programs. In this study, the in vitro antitubercular activity of two novel 1,4-dihydropyridine derivatives (F-27, Cl-33) were screened against a total of 113 different strains of Mycobacterium tub...
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The Journal of Infection in Developing Countries
2017-06-01
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| Series: | Journal of Infection in Developing Countries |
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| Online Access: | https://jidc.org/index.php/journal/article/view/7966 |
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| author | Mehdi Zandhaghighi Farzin Hadizadeh Saman Soleimanpour Zahra Meshkat Seyed Abdolrahim Rezaee Mohammad Derakhshan Kiarash Ghazvini |
| author_facet | Mehdi Zandhaghighi Farzin Hadizadeh Saman Soleimanpour Zahra Meshkat Seyed Abdolrahim Rezaee Mohammad Derakhshan Kiarash Ghazvini |
| author_sort | Mehdi Zandhaghighi |
| collection | DOAJ |
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Introduction: Introducing new and effective antitubercular agents is important in tuberculosis control programs. In this study, the in vitro antitubercular activity of two novel 1,4-dihydropyridine derivatives (F-27, Cl-33) were screened against a total of 113 different strains of Mycobacterium tuberculosis (77 susceptible and 36 resistant clinical isolates).
Methodology: The in vitro activities of these compounds were evaluated based on the modified broth macro-dilution assay.
Results: Compound F-27 showed more than 90% growth inhibition at the range of 2 to 8 μg/mL (minimum inhibitory concentration [MIC]90: 4.13 ± 0.45 µg/mL; p < 0.01), and complete growth inhibition was observed at the range of 8 to 32 μg/mL (minimum bactericidal concentration [MBC]: 11.2 ± 1.65 µg/mL; p < 0.01) against susceptible strains. However, 92% of the resistant strains showed some degree of susceptibility against this compound (MIC90 range: 16 to 64 µg/mL; mean: 40.4 ± 8 µg/mL; p < 0.01). It was found that although there is a linear relationship between the inhibitory activity of F-27 and isoniazid against resistant strains at low concentrations (r = 0.484, p < 0.001), there was no relationship between resistance to isoniazid and F-27 at higher concentrations (r = 0.019, p > 0.1). This may emphasize no cross-resistance between F-27 and isoniazid.
Conclusions: Considering the sufficient sample size of the study and based on the excellent antimycobacterial activity of F-27, it could be concluded that F-27 is a potent candidate as a lead compound, and may be considered for development of a new antitubercular agent.
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| format | Article |
| id | doaj-art-ed0c04bf4498471d95d2e80b31405889 |
| institution | OA Journals |
| issn | 1972-2680 |
| language | English |
| publishDate | 2017-06-01 |
| publisher | The Journal of Infection in Developing Countries |
| record_format | Article |
| series | Journal of Infection in Developing Countries |
| spelling | doaj-art-ed0c04bf4498471d95d2e80b314058892025-08-20T02:27:20ZengThe Journal of Infection in Developing CountriesJournal of Infection in Developing Countries1972-26802017-06-01110610.3855/jidc.7966In vitro bactericidal activities of two novel dihydropyridine derivatives against Mycobacterium tuberculosisMehdi Zandhaghighi0Farzin Hadizadeh1Saman Soleimanpour2Zahra Meshkat3Seyed Abdolrahim Rezaee4Mohammad Derakhshan5Kiarash Ghazvini6Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranSchool of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranFaculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranFaculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranFaculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranFaculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranFaculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Introduction: Introducing new and effective antitubercular agents is important in tuberculosis control programs. In this study, the in vitro antitubercular activity of two novel 1,4-dihydropyridine derivatives (F-27, Cl-33) were screened against a total of 113 different strains of Mycobacterium tuberculosis (77 susceptible and 36 resistant clinical isolates). Methodology: The in vitro activities of these compounds were evaluated based on the modified broth macro-dilution assay. Results: Compound F-27 showed more than 90% growth inhibition at the range of 2 to 8 μg/mL (minimum inhibitory concentration [MIC]90: 4.13 ± 0.45 µg/mL; p < 0.01), and complete growth inhibition was observed at the range of 8 to 32 μg/mL (minimum bactericidal concentration [MBC]: 11.2 ± 1.65 µg/mL; p < 0.01) against susceptible strains. However, 92% of the resistant strains showed some degree of susceptibility against this compound (MIC90 range: 16 to 64 µg/mL; mean: 40.4 ± 8 µg/mL; p < 0.01). It was found that although there is a linear relationship between the inhibitory activity of F-27 and isoniazid against resistant strains at low concentrations (r = 0.484, p < 0.001), there was no relationship between resistance to isoniazid and F-27 at higher concentrations (r = 0.019, p > 0.1). This may emphasize no cross-resistance between F-27 and isoniazid. Conclusions: Considering the sufficient sample size of the study and based on the excellent antimycobacterial activity of F-27, it could be concluded that F-27 is a potent candidate as a lead compound, and may be considered for development of a new antitubercular agent. https://jidc.org/index.php/journal/article/view/7966Drug discoverydihydropyridinesantitubercular agentsdrug evaluationpreclinical |
| spellingShingle | Mehdi Zandhaghighi Farzin Hadizadeh Saman Soleimanpour Zahra Meshkat Seyed Abdolrahim Rezaee Mohammad Derakhshan Kiarash Ghazvini In vitro bactericidal activities of two novel dihydropyridine derivatives against Mycobacterium tuberculosis Journal of Infection in Developing Countries Drug discovery dihydropyridines antitubercular agents drug evaluation preclinical |
| title | In vitro bactericidal activities of two novel dihydropyridine derivatives against Mycobacterium tuberculosis |
| title_full | In vitro bactericidal activities of two novel dihydropyridine derivatives against Mycobacterium tuberculosis |
| title_fullStr | In vitro bactericidal activities of two novel dihydropyridine derivatives against Mycobacterium tuberculosis |
| title_full_unstemmed | In vitro bactericidal activities of two novel dihydropyridine derivatives against Mycobacterium tuberculosis |
| title_short | In vitro bactericidal activities of two novel dihydropyridine derivatives against Mycobacterium tuberculosis |
| title_sort | in vitro bactericidal activities of two novel dihydropyridine derivatives against mycobacterium tuberculosis |
| topic | Drug discovery dihydropyridines antitubercular agents drug evaluation preclinical |
| url | https://jidc.org/index.php/journal/article/view/7966 |
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