Identification of 3-nitro-2, 4, 6-trihydroxybenzamide derivatives as photosynthetic electron transport inhibitors by QSAR and pharmacophore studies.

In the present investigation, QSAR analysis was performed on a data set consist of structurally diverse compounds in order to investigate the role of its structural features on their Photosynthetic Electron Transport Inhibitors. The herbicidal activity co-related with certain topological and hydrophobicity based descriptors, 3D descriptors dependent steric, electrostatic and hydrophobic. The best 2D QSAR model was selected, having correlation coefficient r = 0.8544 and cross validated squared correlation coefficient q = 0.7139 with external predictive ability of pred_r = 0.7753 was developed. The results obtained in this study indicate that hydroxy and nitro groups, as expressed by the SsOHcount, SddsN (nitro) count, is the most relevant molecular property determining efficiency of photosynthetic inhibitory. Molecular field analysis was used to construct the best k-nearest neighbor (kNN-MFA)-based 3DQSAR model using SA-PLS method, showing good correlative and predictive capabilities in terms of q = 0.7694 and pred_r = 0.7381. The influences of steric, electrostatic and hydrophobic field effects generated by the contribution plots are discussed. The pharmacophore model includes three features viz. hydrogen bond donor, hydrogen bond acceptor, and one aromatic feature was developed. The developed model was found to be predictive and can be used to design potent Photosynthetic Electron Transport activities prior to their synthesis for further lead modification. The results obtained suggest that the 3-nitro-2, 4, 6-trihydroxybenzamide analogues represent promising candidates for the development of new active principles targeting photosynthesis to be used as herbicides.