title: Biotransformation of ent-pimaradienoic acid by cell cultures of Aspergillus niger.
abstract: Microbial transformation stands out among the many possible semi-synthetic strategies employed to increase the variety of chemical structures that can be applied in the search for novel bioactive compounds. In this paper we obtained ent-pimaradienoic acid (1, PA, ent-pimara-8(14),15-dien-19-oic acid) derivatives by fungal biotransformation using Aspergillus niger strains. To assess the ability of such compounds to inhibit vascular smooth muscle contraction, we also investigated their spasmolytic effect, along with another five PA derivatives previously obtained in our laboratory, on aortic rings isolated from male Wistar rats. The microbial transformation experiments were conducted at 30°C using submerged shaken liquid culture (120 rpm) for 10 days. One known compound, 7α-hydroxy ent-pimara-8(14),15-dien-19-oic acid (2), and three new derivatives, 1β-hydroxy ent-pimara-6,8(14),15-trien-19-oic acid (3), 1α,6β,14β-trihydroxy ent-pimara-7,15-dien-19-oic acid (4), and 1α,6β,7α,11α-tetrahydroxy ent-pimara-8(14),15-dien-19-oic acid (5), were isolated and identified on the basis of spectroscopic analyses and computational studies. The compounds obtained through biotransformation (2-5) did not display a significant antispasmodic activity (values ranging from 0% to 16.8% of inhibition); however the previously obtained diterpene, methyl 7α-hydroxy ent-pimara-8(14),15-dien-19-oate (8), showed to be very effective (82.5% of inhibition). In addition, our biological results highlight the importance to study the antispasmodic potential of a large number of novel diterpenes, to conduct further structure-activity relationship investigations.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Marcela E
authors.initials: ME
authors.lastname: Severiano
authors.forename: Marília R
authors.initials: MR
authors.lastname: Simão
authors.forename: Henrique P
authors.initials: HP
authors.lastname: Ramos
authors.forename: Renato L T
authors.initials: RL
authors.lastname: Parreira
authors.forename: Nilton S
authors.initials: NS
authors.lastname: Arakawa
authors.forename: Suraia
authors.initials: S
authors.lastname: Said
authors.forename: Niege A J C
authors.initials: NA
authors.lastname: Furtado
authors.forename: Dionéia C R
authors.initials: DC
authors.lastname: de Oliveira
authors.forename: Luis E
authors.initials: LE
authors.lastname: Gregório
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
authors.forename: Rodrigo C S
authors.initials: RC
authors.lastname: Veneziani
authors.forename: Sérgio R
authors.initials: SR
authors.lastname: Ambrósio
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001234:Aspergillus niger / Q000378:metabolism*; D019659:Asteraceae / Q000378:metabolism; D001711:Biotransformation; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008968:Molecular Conformation; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004224:Diterpenes; D010656:Phenylephrine; C008911:pimaric acid
keywords: Antispasmodic property; Aspergillus niger; Biotransformation; ent-Pimaradienoic acid