Nezhun Gören

Inhibition of transcription factor NF-κB by sesquiterpene lactones: a proposed molecular mechanism of action☆

Many sesquiterpene lactones (SLs) possess considerable anti-inflammatory activity. They inhibit the transcription factor NF-kappaB by selectively alkylating its p65 subunit probably by reacting with cysteine residues. Here we assayed 28 sesquiterpene lactones for their ability to inhibit NF-kappaB. The majority of the potent NF-kappaB inhibitors possess two reactive centers in form of an alpha-methylene-gamma-lactone group and an alpha,beta- or alpha,beta,gamma,delta-unsaturated carbonyl group. Based on computer molecular modelling we propose a molecular mechanism of action, which is able to explain the p65 selectivity of the SLs and the observed correlation of high activity with alkylant bifunctionality. A single bifunctional SL molecule can alkylate the cysteine residue (Cys 38) in the DNA binding loop 1 (L1) and a further cysteine (Cys 120) in the nearby E region. This cross link alters the position of tyrosine 36 and additional amino acids in such a way that their specific interactions with the DNA become impossible. We also created a model for monofunctional SLs.

Sesquiterpene lactones from Tanacetum argenteum

Abstract The flowers of Tanacetum argenteum subsp. argenteum yielded two new germacranolides, in addition to some known sesquiterpene lactones. The structures were elucidated by spectral methods and chemical transformations. 8α-Angeloyloxycostunolide showed cytotoxic activity and antifeedant activity against neonate larvae of Spodoptera littoralis .

Sesquiterpene lactones from Tanacetum densum subsp. amani

Abstract In addition to known eudesmanolide and germacranolide sesquiterpene lactones a new eudesmanolide, 1β,4α,6α-trihydroxyeudesm-11-en-8α,12-olide was isolated from the aerial parts of Tanacetum densum subsp. amani . The structure of the new compound was established by spectral data; it showed weak antimicrobial activity.

Sesquiterpenoids from Tanacetum argenteum subsp. canum var. canum

Abstract Aerial parts of Tanacetum argenteum subsp. canum var. canum afforded fourteen sesquiterpene lactones, two of them being new. The new compounds 1β-hydroxy-6α-angeloyloxygermacra-4(5),10(14),11(13)-trien-8,12-olide and 1β,4α-dihydroxy-6α-isobutyloxyeudesm-11(13)-en-8,12-olide, as well as the known ones: parthenolide, peroxyparthenolide, dihyroparthenolide, 1- epi -tatridin B, sivasinolide, flabellin, 1β,4α-dihydroxy-6α-angeloyloxyeudesm-11(13)-en-8,12-olide, 1β-hydroxy-6α-angeloyloxyeudesm-4(15),11(13)-dien-8,12-olide, michelenolide, magnograndiolide, santamarin and douglanin, were identified by spectral methods.

Sesquiterpenes of Tanacetum chiliophyllum var. Heimerlei

Abstract Tanacetum chiliophyllum var. heimerlei afforded nine eudesmanolide and germacranolide type sesquiterpene lactones, two of them being new. The structures were elucidated by spectral methods.

CONSTITUENTS OF TANACETUM DENSUM SUBSP. EGINENSE

Abstract The aerial parts of Tanacetum densum subsp. eginense yielded a new eudesmanolide, some known compounds, nine sesquiterpene lactones, two farnesol derivatives, an aliphatic diterpene, an aromatic compound and two flavonoids. The structures were elucidated by spectral methods.

A guaianolide from Tanacetum argenteum subsp. flabellifolium

Abstract A new guaianolide was isolated from the aerial parts of Tanacetum argenteum subsp. flabellifolium , which is endemic to Turkey. The structure of the new compound was elucidated by spectral methods, including NMR ( 1 H NMR, NOE, APT, DEPT and HETCOR) and X-ray techniques.

Two farnesol derivatives from Tanacetum densum subsp. Sivasicum

Abstract The aerial parts of Tanacetum densum subsp. sivasicum yielded two new farnesol derivatives, 11-hydroxy-5,14-diacetoxy-9,10-dehydrofarnesol acet

A farnesol derivative from Tanacetum aucheranum

Tanacetum aucheranum yielded a new farnesol derivative, 3,10-dihydroxy-5,8-diacetoxy-1(2),11(12)-dehydrojarnesol, and flavonoids. The structures of the compounds were determined by means of spectral methods.

A NEW GERMACRANOLIDE FROM TANACETUM DENSUM SSP SIVASICUM (COMPOSITAE)

Abstract A new germacranolide [1] was isolated from the aerial parts of Tanacetum densum ssp. sivasicum (Compositae), a species endemic to Turkey.