Molecular modeling studies and in vitro screening of dihydrorugosaflavonoid and its derivatives against Mycobacterium tuberculosis. Issue 19 (16th March 2018)

• Record Type: Journal Article
• Authors: Puranik, Ninad V.; Srivastava, Pratibha; Swami, Sagar; Choudhari, Amit; Sarkar, Dhiman
• Is Part Of: RSC advances. Volume 8:Issue 19(2018)
• Page Start: 10634
• Page End: 10643
• Publication Date: 2018-03-16
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c8ra00636a
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Novel drug regimens against tuberculosis (TB) are urgently needed and may be developed by targeting essential enzymes of Mtb that sustain the pathogenicity of tuberculosis. Dihydrorugosaflavonoid interacted with the active pocket of MabA and PanK. Abstract : Novel drug regimens against tuberculosis (TB) are urgently needed and may be developed by targeting essential enzymes of Mtb that sustain the pathogenicity of tuberculosis. In the present investigation, series of compounds (5a–f and6a–f ) based on a naturally occurring rugosaflavonoid moiety were evaluated by in silico molecular modeling studies against β-ketoacyl-ACP reductase (MabA) (PDB ID: IUZN) and pantothenate kinase (PanK) (PDB ID: ;3AF3 ). Compounds5a, 5c, 5d, and6c, which had docking scores of −8.29, −8.36, −8.17 and −7.39 kcal mol −1, respectively, displayed interactions with MabA that were better than those of isoniazid (−6.81 kcal mol −1 ). Similarly, compounds5a, 5c, 5d, and6c, which had docking scores of −7.55, −7.64, −7.40 and −6.7 kcal mol −1, respectively, displayed interactions with PanK that were comparable to those of isoniazid (−7.64 kcal mol −1 ). Because of their docking scores, these compounds were screened in vitro against Mycobacterium tuberculosis H37Ra (Mtb) using an XRMA protocol. Among the screened compounds, the dihydrorugosaflavonoid derivatives5a, 5c, and5d had IC50 values of 12.93, 8.43 and 11.3 μg mL −1, respectively, and exhibited better inhibitory activity than the parent rugosaflavonoid derivatives. The rugosaflavonoid derivative6c had an IC50 value of 17.57 μg mL −1 . The synthesized compounds also displayed inhibitory activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus . The present study will be helpful for the further development of these molecules into antitubercular lead candidates.