A s?ntese e a estrutura cristalina por difra??o de raios-X de dois an?logos de neolignanas, 2-(4-clorofenil)-1-feniletanona (20) e 2-[tio(4-clorofenil)]-1-(3,4-dimetoxifenil)propan-1-ona (12) s?o descritas. O composto 12 apresenta atividade intracelular contra Leishmania donovani e Leishmania amazonensis de amastigotas que causam a leishmaniose tegumentar e visceral. Al?m disso, a teoria do funcional de densidade (DFT) com o funcional h?brido B3LYP foi empregado para calcular um conjunto de descritores moleculares para dezenove an?logos sint?ticos de neolignanas com atividades antileishmaniose. Posteriormente, a an?lise discriminante stepwise foi realizada para investigar poss?veis rela??es entre a estrutura molecular e atividades biol?gicas. Por meio dessa an?lise os compostos foram classificados em dois grupos ativos e inativos de acordo com seu grau de atividade biol?gica, e as propriedades mais importantes foram as cargas de alguns ?tomos, a afinidade eletr?nica e o ClogP. ; ABSTRACT: The synthesis and X-ray crystal diffraction structure of two analogues of neolignans, 2-(4-chlorophenyl)-1-phenylethanone (20) and 2-[(4-chlorophenyl)thio]-1-(3,4-dimethoxyphenyl)propan-1-one (12) is described. The compound 12 presents activity against intracellular Leishmania donovani and Leishmania amazonensis amastigotes that cause cutaneous and visceral leishmaniasis. In addition, the density functional theory (DFT) with the B3LYP hybrid functional was employed to calculate a set of molecular descriptors for nineteen synthetic analogues of neolignans with antileishmanial activities. Afterwards, the stepwise discriminant analysis was performed to investigate possible relationship between the molecular descriptors and biological activities. Through this analysis the compounds were classified into two groups active and inactive according to their degree of biological activities, and the more important properties were charges on some key atoms, electronic affinity and ClogP.