Estudo cristalográfico de isobenzofuran-1(3H)-onas com potencial atividade citotóxica

Abstract

Heterocyclic compounds play an important role in various fields of scientific knowledge, including research and development of pharmaceuticals and agrochemicals. The isobezofuran-1(3H)-ones are biologically active with a wide range of pharmacological activities, including antiparasitic activity, cytotoxicity against cancer cell lines, antiplatelet drugs against cerebral ischemia apoplexy, among others. With the objective to obtain novel compounds and to evaluate the cytotoxic activity against tumor cell lines K562 (myeloid leukemia) and HL60 (leukemia), four isobezofuran-1(3H)-ones functionalized at the C-3 position were synthesized. In this work are shown the results of the structural elucidation by X–ray diffraction, of four novel organic compounds: Compound 1: 3-(2-phenyl-2-oxoethyl)-isobenzofuran-1(3H)-one; Compound 2: 3-[2-(4-methoxyphenyl)-2-oxoethyl)]-isobenzofuran-1(3H)-one; Compound 3: 3-[2-(4-hydroxyphenyl)-2-oxoethyl]-isobenzofuran-1(3H)-one; Compound 4: 3-[2-(4-methylphenyl)-2-oxoethyl]-isobenzofuran-1(3H)-one.

The structures of the compounds 1-4 were elucidated. The results showed that compound 1 crystallize in the orthorhombic system, P212121 non-centrosymmetric space group and the other crystallizes in the monoclinic system in different centrosymmetric space groups. All compounds exhibit two substantially planar regions as follows: (1) isobenzofuranone ring and (2) 2-phenyl-2-oxoethyl. C3 atom of the isobenzofuranones is an asymmetric carbon. Compounds 2, 3 and 4 show in their crystal a racemic mixture (RS). Compound 1 doesn’t present racemic mixture and its absolute structure couldn’t be determined. In the crystal packing of the compounds 1 and 3 were found intramolecular interactions. The crystal of 1 has two intermolecular interactions: one C–H···O and one C–H···. The crystal of 3 presents three intermolecular interactions: one C–H···O, one C–H··· and a classical hydrogen bonding of the kind O–H···O. The crystal packing of the compounds 2 and 4 present one intramolecular interaction and five intermolecular interactions of the kind C– H···O and C–H···.