Crystal structure and molecular docking studies of benzo[8]annulenes as potential inhibitors against Mycobacterium tuberculosis

RA Nagalakshmi, J Suresh, S Maharani, R Ranjith Kumar


Tuberculosis is a disease caused by Mycobacterium tuberculosis. The bacterial cell wall has a characteristic low permeability, which essentially makes antibiotics ineffective. The cell wall material must be regulated so that its deposition does not compromise its structure. In this study, two new inhibitors, 2-amino-4-(4-cholorophenyl)-5,6,7,8,9,10-hexahydrobenzo[8] annulene-1,3,3(4H)-tricarbonitrile(Ia) and 2-amino-4-(4-bromophenyl)-5,6,7,8,9,10-hexahydrobenzo[8]annulene-1,3,3(4H)-tricarbonitrile(Ib) were synthesized. The crystal structures of the above compounds were determined by single crystal X-ray diffraction. The compounds C21 H19 Cl N3 (Ia) and C21 H19 Br N3 (Ib) were crystallized in the monoclinic and triclinic system. In both compounds, the cyclohexane ring was found to adopt a boat conformation. The cyclooctane ring of both compounds adopted a twisted chair-chair conformation.  In silico analyses revealed that both compounds showed good anti-mycobacterial activities against the enoyl-acyl carrier enzyme and the N-acetyl-gamma protein, both of which are critical for bacterial survival. Synthesis, structure determination, conformation, intra, inter-molecular interactions and docking studies of both compounds are presented herein.


conformation; ring motif; anti-mycobacterial; molecular docking; mycobacterium tuberculosis; benzo[8]annulenes; crystal structure


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