Synthesis, Docking, and Pharmacological Evaluation of Derivatives of α‐Aminoketones Appended to Sydnones as Potent Antitubercular and Antifungal Scaffolds

3‐Arylsydnones are reported to possess striking pharmaceutical potency. α‐Aminoketone, a biologically active structural unit, is built at the fourth (electrophilic) position of sydnone and further derivatized with secondary amine and tetrazoles. The α‐aminoketone derivatives of sydnones coupled with...

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Bibliographic Details
Published in:Journal of heterocyclic chemistry 2019-09, Vol.56 (9), p.2430-2441
Main Authors: Dorababu, Atukuri, Kamble, Ravindra R., Shaikh, Saba Kauser J., Somagond, Shilpa M., Bayannavar, Praveen K., Joshi, Shrinivas D.
Format: Article
Language:English
Subjects:
Amines
Chemical bonds
Crystallography
Derivatives
Docking
Fourier transforms
Fungicides
Hydrogen bonding
Infrared analysis
NMR
Nuclear magnetic resonance
Reductases
Streptomycin
Tetrazoles
Tuberculosis
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Summary:3‐Arylsydnones are reported to possess striking pharmaceutical potency. α‐Aminoketone, a biologically active structural unit, is built at the fourth (electrophilic) position of sydnone and further derivatized with secondary amine and tetrazoles. The α‐aminoketone derivatives of sydnones coupled with secondary amines 4a–n were docked on enoyl acyl carrier protein (ACP) reductase from Mycobacterium tuberculosis, which revealed that compounds 4b, 4f, and 4i showed efficient C score values with different binding modes and hydrogen bonding. Further, these compounds were screened for antimycobacterial activity; among them, compound 4f displayed sensitivity at 6.25 μg/mL compared with the standard drug (Streptomycin) against M. tuberculosis (H37RV strain). In addition to this, α‐aminoketone derivatives of sydnones coupled with tetrazoles 8a–h were evaluated for antifungal activity. In the antifungal activity, compound 8b has exhibited potent activity at 6.25 μg/mL against Candida albicans and compound 8g at 0.4 μg/mL against Aspergillus fumigatus. The antifungal activities are comparatively better than standard antifungal agent Fluconazole at these drug concentrations. Alongside characterization of the final compounds by Fourier transform infrared, mass, 1H NMR, and 13C NMR spectral analyses, compounds 8b and 8g were confirmed by X‐ray crystallographic studies.
ISSN:0022-152X
1943-5193
DOI:10.1002/jhet.3630