New resveratrol (trans-3,4’,5-trihydroxystilbene) analogs were synthesized and screened for their in vitro cancer chemopreventive potential using various bioassays relevant for the prevention of carcinogenesis in humans: Two assays to detect modulators of carcinogen metabolism (Cyp1A inhibition; determination of NAD(P)H/quinone reductase (QR) activity), three assays to identify radical scavenging and antioxidant properties (DPPH, ORAC, superoxide anion radicals in differentiated HL-60 cells), four assays to determine anti-inflammatory and anti-hormonal effects (iNOS, Cox-1 and aromatase inhibition, anti-estrogenic potential). 3,40,5-Tri-O-methyl resveratrol 1a was about seven-fold more active than resveratrol in inhibiting Cyp1A activity, it was a potent inducer of QR activity, and it showed pure anti-estrogenic activity (whereas resveratrol is a known mixed estrogen (ant)agonist with both estrogenic and anti-estrogenic properties). Dual estrogen ant-/agonist activity was restored in the mono-O-benzyl-substituted derivatives 4b (40-O-benzyl resveratrol) and 5b (3-O-benzylresveratrol). With respect to aromatase inhibition (Cyp19), which provided the highest number of actives, the benzyl-substituted series was more potent than the methyl-substituted derivatives of resveratrol, and 3-O-benzyl resveratrol 5b was about eightfold more active than resveratrol. Overall, 21 3,40,5-tri-O-pivaloyl resveratrol oxide 7c was identified as a potent inducer of phase 2 enzymes 22 concomitant with inhibition of LPS-mediated iNOS induction.

Synthesis of resveratrol derivatives and in vitro screening for potential cancer chemopreventive activities / F. Orsini, L. Verotta, K. Klimo, C. Gerhauser. - In: ARCHIV DER PHARMAZIE. - ISSN 0365-6233. - 349:1(2016), pp. 414-427. [10.1002/ardp.201600022]

Synthesis of resveratrol derivatives and in vitro screening for potential cancer chemopreventive activities

F. Orsini
Primo
;
L. Verotta
Secondo
;
2016

Abstract

New resveratrol (trans-3,4’,5-trihydroxystilbene) analogs were synthesized and screened for their in vitro cancer chemopreventive potential using various bioassays relevant for the prevention of carcinogenesis in humans: Two assays to detect modulators of carcinogen metabolism (Cyp1A inhibition; determination of NAD(P)H/quinone reductase (QR) activity), three assays to identify radical scavenging and antioxidant properties (DPPH, ORAC, superoxide anion radicals in differentiated HL-60 cells), four assays to determine anti-inflammatory and anti-hormonal effects (iNOS, Cox-1 and aromatase inhibition, anti-estrogenic potential). 3,40,5-Tri-O-methyl resveratrol 1a was about seven-fold more active than resveratrol in inhibiting Cyp1A activity, it was a potent inducer of QR activity, and it showed pure anti-estrogenic activity (whereas resveratrol is a known mixed estrogen (ant)agonist with both estrogenic and anti-estrogenic properties). Dual estrogen ant-/agonist activity was restored in the mono-O-benzyl-substituted derivatives 4b (40-O-benzyl resveratrol) and 5b (3-O-benzylresveratrol). With respect to aromatase inhibition (Cyp19), which provided the highest number of actives, the benzyl-substituted series was more potent than the methyl-substituted derivatives of resveratrol, and 3-O-benzyl resveratrol 5b was about eightfold more active than resveratrol. Overall, 21 3,40,5-tri-O-pivaloyl resveratrol oxide 7c was identified as a potent inducer of phase 2 enzymes 22 concomitant with inhibition of LPS-mediated iNOS induction.
Aromatase; Chemoprevention; COX-1; Drug metabolism; iNOS; Nrf2; ORAC; Resveratrol
Settore CHIM/06 - Chimica Organica
2016
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/385881
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