Design, synthesis, molecular docking, qsar, antibacterial activity studies of novel tetrahydrocarbazole derivatives

The heterocyclic compound tetrahydrocarbazole and its derivatives are reported to possess varied biological activities.. The enzyme, namely GlcN-6-P synthase, (L-glutamine: D-fructose-6P amidotransferase, PDB CODE:1XFF), also known under the trivial name of glucosamine-6-phosphate synthase, is a new target for antimicrobials. It is a protein synthesis inhibitor in bacteria. It binds to a small 16s rRNA of the 30s subunit of the bacterial ribosome interfering with the binding of formyl – methionyl - tRNA to the 30s subunit. The present investigations is aimed to synthesize some new 1,2,3,4-tetrahydrocarbazoles and further to evaluate them for their antibacterial activity by using agar cup plate method, QSAR will be studied further. The eleven compounds of scheme were subjected to molecular docking studies. The compounds TH1, TH2, TH3, TH4, TH5, TH6, TH8, TH9, TH10 and TH11 showed good negative dock scores. All the N-substituted (tosyl, 4- substituted benzoyl) have shown good negative dock scores with range of -4.3489 to -4.7634. The antimicrobial activity shown by the compounds were less when compared to the standared drugs (ciprofloxacine, fluconazole). The results obtained were statistically analyzed by 3D-QSAR method and found that the PLSR (KNN,MLR) method for 3D- QSAR gave the best results . The predicted values were r2 = 0.9977, q2 = 0.0882, F- test- 1709, Pred_ r2 = -3.309 and Pred_ r2 se=-1.66. The compounds which are having tosyl have shown good docking scores and potential anti microbial activity (TH1, TH2, TH3, TH4, TH5, TH6, TH11,). The compounds which are having electron donating groups such as methyl on benzoyl nucleus attached to the nitrogen atom of tetrahydrocarbazole have shown good dock scores with good antimicrobial activity.