| A series of 51 compounds [N-(substituted-benzylidene)- -carboline-3-carbohydrazide derivatives having significant
inhibitory activity against cancer cell lines was selected and the presented biological activity (in micromolar concentration)
of those compounds were conveniently converted into Log (1/IC50) values (molar) for carrying out QSAR analysis against
anti-cancer activities using Chemoffice Ultra version 7.0.1, from Cambridge software corporation. The values of related
parameters of all the molecules were calculated after effective energy minimization through MM2, MOPAC force fields
provided by Chem3D Ultra 7.0.1. The best QSAR model obtained was taken into consideration on the basis of high Q2
value, which reveals that in order to increase the biological activity, the properties like Log P, and Charge-dipole energy
should be increased, whereas Bending energy which is showing a negative value in the equation should be decreased. Thus,
it is concluded that the biological activity will be increased if substituents that bring about changes in the molecule as
mentioned above are attached to it. As per the given QSAR data, a new series of 1-substituted ?-carboline derivatives
(1a1k) were synthesized having increased LogP value. These title compounds containing seven different substituents at C-1
were screened for their invitro anti-cancer and Anti-microbial activity. Most of the test compounds were found to exhibit
significant anti-cancer activity. Among the substituents at C-1, isopropyl substituent showed maximum potency, while npropyl substituent showed equipotent activity remaining substituents exhibited least activity when compare to other
substituents. The order of activity at C-1 is as understood by QSAR factor (Compound 1e) was found to be the most active
agent which showed highest percentage of cell inhibition against all the cancer cell lines in the minimum concentration,
which have isopropyl group at the 1st position in the ?-carboline nucleus. Hence this molecule can be selected as a lead
molecule of the present study for further exploitationddd |
