Affiliation:
1. P.G. Department of Chemistry and Research Centre, Padmashri Vikhe Patil College, Pravaranagar- 413713, India
2. Organic Chemistry Division Combichem-Bioresource Centre, National Chemical Laboratory, Pune-7, India
3. Y.B.Chavan College of Pharmacy, Aurangabad-431001, India
4. Sinhgad Technical Education Society's Smt. Kashibai Navale College of Pharmacy, Pune-Saswad Road, Kondhwa (Bk), Pune-411048, India
Abstract
A series of side chain modified structurally diverse 3,4-dihydro-2H-benzo[b][1,4]-oxazine-2-carboxylic
acid derivatives were synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral
study. All the newly synthesized compounds were examined for their in vitro antitubercular activity
against Mycobacterium tuberculosis H37Ra. The synthesized compounds exhibited minimum inhibitory
concentration (IC50) ranging from 5.98 to >30 (μg/mL) against MtbH37Ra. Among the screened
compounds, compounds 5a, 5c, 5d, 5f, 5g, 5h, 5I, 5j exhibited IC50 as 10.42, 11.81, 18.79, 5.98,
19.21, 24.81 and 14.81 μg/mL, respectively. The antibacterial screening study of these compounds
was conducted against four different bacteria to asses there selectivity towards MTB. The antibacterial
screening of all the synthesized compounds was conducted against four bacterial strains (Gram-negative
strains: E.coli and S.aureus; Gram-positive strains: P. aeruginosa and B.subtilis. The compounds 5a,
5b, 5c, 5e and 5j showed higher antibacterial activity up to 7-25 μg/mL. Furthermore, molecular
docking studies revealed the binding modes of the compounds in the binding site of the good agreement
with the in vitro antitubercular screening. The compounds 5a, 5c and 5f with free energy of binding
lower than -9.0 Kcal/mol binds more favourably at the binding site of panC as compared to other
compounds. Specifically, the compound 5f with free energy of binding -9.6 Kcal/mol is indeed found
more active in docking study as well as in the in vitro antitubercular screening. These findings open
the possibility for potential lead for antituberculosis chemotherapy.
Publisher
Asian Journal of Chemistry