Purushottamachar Puranik - 3D-QSAR of N-myristoyltransferase inhibiting antifungal agents by CoMFA and CoMSIA methods.

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      Publication Details (including relevant citation   information):

      Bioorg Med Chem. 2003   Aug 5;11(16):3487-97.


      A series of benzofuran antifungals was examined to determine the   structural requirements of N-myristoyltransferase (Nmt) enzyme   inhibition by three-dimensional quantitative structure-activity   relationship (3D-QSAR) using comparative molecular field analysis   (CoMFA) and comparative molecular similarity indices analysis   (CoMSIA) methods. Evaluation of 20 compounds (training set)   served to establish the model, which was validated by evaluation   of a set of 6 compounds (test set). The lowest energy conformer   of the most active molecule obtained from systematic search was   used as the template structure for the alignment. The best   predictions were obtained with the CoMFA model from RMS fit, with   r(2)(cv)=0.828, r(2)(conv)=0.989, r(2)(pred)=0.754 and with the   CoMSIA model combining hydrophobic, hydrogen bond donor and   hydrogen bond acceptor fields with r(2)(cv)=0.821,   r(2)(conv)=0.978 and r(2)(pred)=0.747. The models obtained from   the present study can be useful for the development of new Nmt   inhibitors as potential antifungals. The docking studies were   also carried out wherein the active and inactive molecules were   docked into the active site of the recently reported Candida   albicans Nmt (CaNmt) crystal structure to analyze   enzyme-inhibitor interactions. The results obtained from the   present 3D-QSAR and docking studies were found complimentary.



      Address (URL): http://http://www.ncbi.nlm.nih.gov/pubmed/12878142