TY  - JOUR
A1  - Riad, Noura M.
A1  - Zlotos, Darius P.
A1  - Holzgrabe, Ulrike
T1  - Crystal structure of 5,11-dihydropyrido[2,3-b][1,4]benzodiazepin-6-one.
JF  - Acta Crystallographica Section E Crystallographic Communications
N2  - The title compound, C\(_{12}\)H\(_{9}\)N\(_{3}\)O, is an inter­mediate in the synthesis of the muscarinic M2 receptor antagonist AFDX-384. The seven-membered ring adopts a boat conformation and the dihedral angle between the planes of the aromatic rings is 41.51 (9)°. In the crystal, mol­ecules are linked into [001] chains of alternating inversion dimers formed by pairs of N-H・・・O hydrogen bonds and pairs of N-H・・・N hydrogen bonds. In both cases, R\(_{2}\)\(^{2}\)(8) loops are generated.
KW  - crystal structure
KW  - pyridobenzodiazepine
KW  - boat conformation
KW  - hydrogen bonding
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149627
VL  - E71
ER  - 
TY  - JOUR
A1  - Masic, Anita
A1  - Valencia Hernandez, Ana Maria
A1  - Hazra, Sudipta
A1  - Glaser, Jan
A1  - Holzgrabe, Ulrike
A1  - Hazra, Banasri
A1  - Schurigt, Uta
T1  - Cinnamic Acid Bornyl Ester Derivatives from Valeriana wallichii Exhibit Antileishmanial In Vivo Activity in Leishmania major-Infected BALB/c Mice
JF  - PLoS One
N2  - Human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by Leishmania major or Leishmania donovani, respectively. Some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. Here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileishmanial activity. Good selectivity and antileishmanial activity of bornyl 3-phenylpropanoate (2) in vitro prompted the antileishmanial assessment in vivo. For this purpose, BALB/c mice were infected with Leishmania major promastigotes and treated with three doses of 50 mg/kg/day of compound 2. The treatment prevented the characteristic swelling at the site of infection and correlated with reduced parasite burden. Transmitted light microscopy and transmission electron microscopy of Leishmania major promastigotes revealed that compounds 1 and 2 induce mitochondrial swelling. Subsequent studies on Leishmania major promastigotes showed the loss of mitochondrial transmembrane potential (ΔΨm) as a putative mode of action. As the cinnamic acid bornyl ester derivatives 1 and 2 had exhibited antileishmanial activity in vitro, and compound 2 in Leishmania major-infected BALB/c mice in vivo, they can be regarded as possible lead structures for the development of new antileishmanial therapeutic approaches.
KW  - leishmania major
KW  - promastigotes
KW  - apoptosis
KW  - mitochondria
KW  - parasitic diseases
KW  - leishmania
KW  - leishmaniasis
KW  - mouse models
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125354
VL  - 10
IS  - 11
ER  - 
TY  - JOUR
A1  - Glaser, Jan
A1  - Schurigt, Uta
A1  - Suzuki, Brian M.
A1  - Caffrey, Connor R.
A1  - Holzgrabe, Ulrike
T1  - Anti-Schistosomal Activity of Cinnamic Acid Esters: Eugenyl
JF  - Molecules
N2  - Bornyl caffeate (1) was previously isolated by us from Valeriana (V.) wallichii rhizomes and identified as an anti-leishmanial substance. Here, we screened a small compound library of synthesized derivatives 1–30 for activity against schistosomula of Schistosoma (S.) mansoni. Compound 1 did not show any anti-schistosomal activity. However, strong phenotypic changes, including the formation of vacuoles, degeneration and death were observed after in vitro treatment with compounds 23 (thymyl cinnamate) and 27 (eugenyl cinnamate). Electron microscopy analysis of the induced vacuoles in the dying parasites suggests that 23 and 27 interfere with autophagy.
KW  - thymyl cinnamate
KW  - vacuoles
KW  - autophagy
KW  - anti-schistosomal activity
KW  - schistosoma
KW  - schistosomula
KW  - parasite
KW  - eugenyl cinnamate
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125712
VL  - 20
ER  - 
TY  - JOUR
A1  - Glaser, Jan
A1  - Schultheis, Martina
A1  - Moll, Heidrun
A1  - Hazra, Banasri
A1  - Holzgrabe, Ulrike
T1  - Antileishmanial and Cytotoxic Compounds from Valeriana wallichii and Identification of a Novel Nepetolactone Derivative
JF  - Molecules
N2  - The chloroform extract of Valeriana wallichii (V. wallichii) rhizomes was investigated to elucidate the structures responsible for reported antileishmanial activity. Besides bornyl caffeate (1, already been reported by us previously), bioassay-guided fractionation resulted in two additional cinnamic acid derivatives 2–3 with moderate leishmanicidal activity. The structure of a novel nepetolactone derivative 4 having a cinnamic acid moiety was elucidated by means of spectral analysis. To the best of our knowledge villoside aglycone (5) was isolated from this plant for the first time. The bioassay-guided fractionation yielded two new (compounds 6–7) and two known valtrates (compounds 8–9) with leishmanicidal potential against Leishmania major (L. major) promastigotes. In addition, β-bisabolol (10), α-kessyl alcohol (11), valeranone (12), bornyl isovalerate (13) and linarin-2-O-methylbutyrate (14) were identified. This is the first report on the isolation of 4'-demethylpodophyllotoxin (15), podophyllotoxin (16) and pinoresinol (17) in V. wallichii. In total thirteen known and four new compounds were identified from the extract and their cytotoxic and antileishmanial properties were evaluated.
KW  - novel nepetolactone derivative
KW  - cytotoxicity
KW  - antileishmanial
KW  - V. wallichii
KW  - podophyllotoxin
KW  - valtrates
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125320
VL  - 20
IS  - 4
ER  -