title: SYNTHESIS AND BIOLOGICAL ACTIVITY OF SULFUR COMPOUNDS SHOWING STRUCTURAL ANALOGY WITH COMBRETASTATIN A-4.
abstract: We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones withm-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15).
authors.affiliation: Departamento de Química, Universidade Federal de Mato Grosso do Sul, Av. Senador Filinto Müller, 1555, 79074-460 Campo Grande - MS, Brasil.
authors.forename: Edson Dos A
authors.initials: ED
authors.lastname: Dos Santos
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Prado
authors.forename: Wanderley R
authors.initials: WR
authors.lastname: de Carvalho
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: de Lima
authors.forename: Adilson
authors.initials: A
authors.lastname: Beatriz E
authors.forename: Dênis P
authors.initials: DP
authors.lastname: de Lima
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.forename: Marzena A
authors.initials: MA
authors.lastname: Dyba
authors.forename: Sergio
authors.initials: S
authors.lastname: Albuquerque
keywords: antitubulin activity; combretastatin A-4; leishmanicidal activity