Structural factors affecting cytotoxic activity of (E)-1-(Benzo[d ][1,3]oxathiol-6-yl)-3-phenylprop-2-en-1-one derivatives.
Derivatives of (E)-1-(5-alkoxybenzo[d][1,3]oxathiol-6-yl)-3-phenylprop-2-en-1-one demonstrated exceptionally high in vitro cytotoxic activity, with IC50 values of the most active derivatives in the nanomolar range. To identify structural fragments necessary for the activity, several analogs deprived of selected fragments were prepared, and their cytotoxic activity was tested. It was found that the activity depends on combined effects of (i) the heterocyclic ring, (ii) the alkoxy group at position 5 of the benzoxathiole ring, and (iii) the substituents in the phenyl ring B. Replacement of the sulfur atom by oxygen does not influence the activity. None of the listed structural fragments alone assured high cytotoxic activity.
Department of Chemical Technology of Drugs, Medical University of Gdansk, 80-416, Gdansk, Poland.
Marek T
MT
Konieczny
Anita
A
Bułakowska
Justyna
J
Polak
Danuta
D
Pirska
Wojciech
W
Konieczny
Patrycja
P
Gryń
Andrzej
A
Skladanowski
Michał
M
Sabisz
Krzysztof
K
Lemke
Anna
A
Pieczykolan
Marlena
M
Gałązka
Katarzyna
K
Wiciejowska
Joanna
J
Wietrzyk
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D047188:Chalcones; D013438:Sulfhydryl Compounds; C008730:oxathiol
SAR; benzoxathiole; chalcone; cytotoxic activity; structure optimization