title: Bismuth heterocycles based on a diphenyl sulfone scaffold: synthesis and substituent effect on the antifungal activity against Saccharomyces cerevisiae.
abstract: A series of heterocyclic organobismuth(III) compounds 2 [ClBi(5-R-C6H(3)-2-SO2C6H(4)-1'-): R=Me, Ph, MeO, Cl, H, t-Bu, CF3, F, Me2N] was synthesized in order to study the relative importance of structure and specific substitutions in relation to their lipophilicity and antifungal activity against the yeast Saccharomyces cerevisiae. A clear structure-activity relationship between the size of the inhibition zone and the value of ClogP was found for 2. These results suggest that the higher the lipophilicity, the lower the antifungal activity. Thus, 2e (R=H) and 2h (R=F), which had ClogP values of 1.18 and 1.45, respectively, were most active. In contrast, 2b (R=Ph) and 2f (R=t-Bu) had ClogP values of 3.06 and 3.00, respectively, and exhibited no antifungal activity. Compound 6b ClBi[5-(OH)C6H(3)-2-SO(2)-5'-(OH)C6H(3)-1'-] had an estimated ClogP value of 0.81 but exhibited only low activity in spite of its low ClogP value, suggesting that such a considerable decrease in lipophilicity lowers inhibition activity. Bismuth carboxylate 7b derived from p-nitrobenzoic acid and 2e exhibited inhibition activity comparable to those of 2e and 2h despite its higher lipophilicity (ClogP=2.68).
authors.affiliation: Graduate School of Medicine, Department of Chemistry, Faculty of Science, Yamaguchi University, Yamaguchi 753-8512, Japan. murafuji@yamaguchi-u.ac.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Murafuji
authors.forename: Yudai
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshimatsu
authors.forename: Isamu
authors.initials: I
authors.lastname: Miyakawa
authors.forename: Kouto
authors.initials: K
authors.lastname: Migita
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mikata
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001729:Bismuth / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D013450:Sulfones; D001729:Bismuth