Borontribromide-mediated C–C bond formation in cyclic ketones: a transition metal free approach†

Imran Ahmad, Vinay Pathak,a Prema G. Vasudev,b Hardesh K. Mauryaa
and Atul Gupta*a
RSC Adv., 2014, 4, 24619

Borontribromide (BBr3) is a well-known demethylating agent. The current investigation was focused on a new application of borontribromide as a C–C bond forming agent in cyclic ketones. In this study, borontribromide mediated C–C bond formation reactions of tetralones, chromenone, thiochromenone and indanones were explored. A methoxy group containing ketones showed selective C–C bond formation reaction instead of demethylation of the methoxy group. MM2 steric energy calculations for the final products showed that the reaction favored the formation of exo- or endo-cyclic double bond containing products, depending upon their low MM2 steric energy in a specific frame structure, as observed in X-ray crystallography. A comprehensive crystallographic and pi-stacking analysis of product 10a demonstrated the formation of 10a as an enantiomeric mixture, and its centre of inversion was stabilized by a set of three unique pi–pi interactions.

QSAR and docking studies on chalcone derivatives for antitubercular activity against M. tuberculosis H37Rv

JOURNAL OF CHEMOMETRICS

Dharmendra Kumar Yadav, Imran Ahmad, Aparna Shukla, Feroz Khan, Arvind Singh Negi and Atul Gupta

DOI: 10.1002/cem.2606

Keywords:

• chalcones;
• QSAR;
• docking;
• M. tuberculosis H₃₇Rv;
• enoyl reductase;
• ADMET

In our prior studies, we reported some known antitubercular drugs (rifampicin and streptomycin) and newly synthesized chalcone derivatives (16–26) tested in vitro against Mycobacterium tuberculosis H₃₇Rv strain. Most of the tested compounds were efficient antimycobacterial agents showing minimum inhibitory concentration values ranging from 3.5 to 30 µg mL⁻¹. In the present work, a quantitative structure–activity relationship (QSAR) study has been performed on these active chalcone derivatives to correlate their chemical structures with their observed inhibiting activity against M. tuberculosis. A QSAR model that is able to correlate well the antitubercular activity with the chemical structures of active chalcone derivatives 16, 24, 25a, 25c, and 26 has been developed, which is potentially helpful in the design of novel and more potent antitubercular agents. The r² and rCV² of a newly derived QSAR model were 0.89 and 0.84, respectively. The QSAR study indicates that chemical properties, viz. heat of formation (kcal mol⁻¹), lowest unoccupied molecular orbital energy (eV), and amine, hydroxyl, and methyl groups counts, correlate well with the activity. In silico screening results for oral bioavailability and absorption, distribution, metabolism, excretion, and toxicity compliance showed that compounds 25a, 25c, and 24 were found active similar to rifampicin and streptomycin. The docking study for the exploration of mechanism of action showed high binding affinity of active derivatives. 

Syntheses of lipophilic chalcones and their conformationally restricted analogues as antitubercular agents

Bioorganic & Medicinal Chemistry Letters, Volume 23, Issue 5, 1 March 2013, Pages 1322-1325





Imran Ahmad, Jay Prakash Thakur, Debabrata Chanda, Dharmendra Saikia, Feroz Khan, Shivani Dixit, Amit Kumar, Rituraj Konwar, Arvind Singh Negi, Atul Gupta

Graphical abstract

Lipophilic chalcones and their conformationally restricted analogues were synthesized and evaluated for their antitubercular efficacy against Mycobacterium tuberculosisH37Rv strain. Compounds 16, 24, 25a and 25c were found to be active MIC at 60, 30, 3.5 and 7.5 μg-mL⁻¹. In vitro cytotoxicity of compounds 16, 24, 25a, 25c and 26 in non-cancerous human epithelial kidney cell line (HEK-293) showed that most active compound 25a was approximately 2.85 times selective towards tubercular versus healthy cells whereas compound 24 was found to be 16 times selective.