title: Structural requirements for the antifungal activities of natural drimane sesquiterpenes and analogues,  supported by conformational and electronic studies.
abstract: Seventeen drimanes including polygodial (1), isopolygodial (2), drimenol (3) and confertifolin (4) obtained from natural sources and the semi-synthetic derivatives 5-17 obtained from 1-3, were evaluated in vitro for antifungal properties against a unique panel of fungi with standardized procedures by using two end-points, MIC(100) and MIC(50). A SAR analysis of the whole series, supported by conformational and electronic studies, allowed us to show that the Δ7,8 -double bond would be one of the key structural features related to the antifungal activity. The MEPs obtained for active compounds exhibit a clear negative minimum value (deep red zone) in the vicinity of the Δ7,8 -double bond, which is not present in the inactive ones. Apart of this negative zone, a positive region (deep blue) appears in 1, which is not observed either in its epimer 2 nor in the rest of the active compounds. The LogP of active compounds varies between 2.33 and 3.84, but differences in MICs are not correlated with concomitant variations in LogP values.
authors: Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
authors: Marcos
authors: M
authors: Derita
authors: Iván
authors: I
authors: Montenegro
authors: Francisco
authors: F
authors: Garibotto
authors: Ricardo D
authors: RD
authors: Enriz
authors: Mauricio Cuellar
authors: MC
authors: Fritis
authors: Susana A
authors: SA
authors: Zacchino
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology*; D004583:Electrons; D005658:Fungi / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D000081223:Polycyclic Sesquiterpenes; D028502:Polygonum / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000935:Antifungal Agents; D001688:Biological Products; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C437376:drimane
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