Synthesis and biological evaluation of novel sulfonanilide compounds as antiproliferative agents for breast cancer.
Combinatorial chemistry approaches facilitate drug discovery processes and result in structural modifications of lead compounds that enhance pharmacological activity, improve pharmacokinetic properties, or reduce unwanted side effects. Epidemiological and animal model studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) can act as chemopreventive agents. The cyclooxygenase-2 (COX-2) inhibitor nimesulide shows anticancer effects in several cancer cell lines via COX-2-dependent and -independent mechanisms. The molecular structure of nimesulide was used as a starting scaffold to design novel sulfonanilide analogs and examine the structural features that contribute to this anticancer effect. A systematic combinatorial chemical approach was used to generate diversely substituted sulfonanilide derivatives that were tested for their effects on the proliferation of human breast cancer cells. Structure-function analysis indicated that the inhibition of cell growth by compounds derived from the novel sulfonanilides required a bulky terminal phenyl ring, a methanesulfonamide, and a hydrophobic carboxamide moiety.
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Bin
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Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, 500 West 12th Avenue, The Ohio State University, Columbus, OH 43210, USA.
Darby
Michael V
MV
Brueggemeier
Robert W
RW
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D013449:Sulfonamides