S. Subramanian (PG),
Departamento de Química, CCEN, Universidade Federal da Paraíba, PB, Brazil
Márcia M. C. Ferreira (PQ)
Departamento de Físico-Química, Instituto de Química, UNICAMP, Campinas, SP, Brazil
=and Milan Trsic (PQ)
Departamento de Química e Física Molecular, Instituto de Química de São Carlos, USP,
=São Carlos, SP, Brazil
 

Keywords: MNDO-AM1-SCF-MO; Lapachol; PCA, HCA, KNN, SIMCA.

          AM1 semiempirical molecular orbital calculations  were  carried out  on  lapachol  and
several  derivatives  of  1,4-naphthoquinone   in  order  to  investigate  possible  relationships
between  electronic structural parameters  and  activity  against  carcinosarcoma  Walker 256
(W256).   It was found  that,  among the calculated electronic indices,  the  HOMO  (highest
occupied molecular orbital) coefficients for carbon atoms of the side-chain double bond have
a significant influence in the activity, while the LUMO (lowest unoccupied molecular orbital)
apparently have no importance.
          Exploratory   data   analysis   through   hierarchical   cluster    (HCA)   and   principal
component analysis  (PCA)  showed  a clear separation of  the  active compounds  from  the
inactive  ones.  The  activity  against  W256  probably  involves  a  mechanism  wherein  the
quinone acts as a  reducing  agent through the partition of the  p-electrons  of the  side-chain
double bond.  A classification study with respect to structure-activity using  KNN (K-nearest
neighbors)  and  SIMCA  (soft  independent  modeling  of  class  analogy),  two  established
chemometric methods of pattern recognition,  have been used  to predict activity for another
series of  lapachol derivatives.