Kamal Aziz Ketuly

Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid

Background Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3′H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats. Methodology/Principal Finding Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes. Conclusion/Significance The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.

Chisomicines A-C, limonoids from Chisocheton ceramicus.

Three new limonoids, chisomicines A-C (1-3), have been isolated from the bark of Chisocheton ceramicus. Their structures were determined by 2D NMR, CD spectroscopic methods, and X-ray analysis. Chisomicine A (1) exhibited NO production inhibitory activity in J774.1 cells stimulated by LPS dose-dependently at high cell viability.

Boronate derivatives of functionally diverse catechols: Stability studies

Benzeneboronate of catecholic carboxyl methyl esters, N-acetyldopamine, coumarin and catechol estrogens were prepared as crystalline derivatives in high yield. Related catechol compounds with extra polar functional group(s) (OH, NH2) do not form or only partially form unstable cyclic boronate derivatives.

Engineering robust polar chiral clathrate crystals

The R-(+)-enantiomeric form of Dianins compound and the S-(+)-enantiomeric form of its direct thiachroman analogue both obtained chromatographically employing a cellulose tris(3,5-dimethylphenylcarbamate) column, are shown to undergo supramolecular assembly to form a polar clathrate lattice which is stable even in the absence of a consolidating guest component.

3β-Acet­oxy-6-hy­droxy­imino­cholestane

Two independent molecules comprise the asymmetric unit of the title cholestane derivative, C29H49NO3 {systematic name: (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-6-hydroxyimino-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate}. The major differences between the molecules relate to the relative orientations of the terminal acetyl [C—C—O—C torsion angles = −158.8 (3) and −81.7 (3)°] and alkyl groups [C—C—C—C = 168.9 (3) and 65.8 (4)°]. In the crystal, the independent molecules associate via pairs of O—H⋯N hydrogen bonds, forming dimeric aggregates. Supramolecular layers in the ab plane are mediated by C—H⋯O interactions.

3-Methyl-5α-cholest-2-ene

In the title cholestane derivative, C28H48 [systematic name: (1S,2S,7R,10R,11R,14R,15R)-2,5,10,15-tetramethyl-14-[(2R)-6-methylheptan-2-yl]tetracyclo[8.7.0.02,7.011,15]heptadec-4-ene], the cyclohexene ring adopts a half-chair conformation. The parent 5α-cholest-2-ene and the equivalent fragment of the title compound are almost superimposable (r.m.s. deviation = 0.033 Å).

(20R,24R,25S)-3α,7α,12α,27-Tetra-acet-oxy-24,26-ep-oxy-5β-cholestane.

In the title anhydroscymnol tetraacetate, C35H54O9, the fused chair conformation of the cyclohexane A/B ring junction is cis with a 5β-H configuration. The compound has a trimethylene oxide ring at position 24,26 and four acetate groups at the 3α,7α,12α,27 positions.

2-Bromo­beclometasone dipropionate

In the crystal structure of 2-bromobeclometasone dipropionate [systematic name: (8S,9R,10S,11S,13S,14S,16S,17R)-2-bromo-9α-chloro-11-hydroxy-10,13,16-trimethyl-3-oxo-17-[2-(propionyloxy)acetyl]-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate], C28H36BrClO7, the six-membered ring with the 1,4-diene-3-one composition is planar (r.m.s. deviations = 0.03 and 0.04 Å for the two independent molecules), whereas the remaining six-membered rings have chair conformations. Each of the independent molecules self-associates via O—H⋯Opropionate hydrogen bonding, generating a supramolecular chain running along the b axis. The crystal is twinned, with the monoclinic unit cell emulating an orthorhomic crystal system; the major twin component constitutes approximately 60%.

9α-Bromo analog of beclometasone dipropionate monohydrate.

In the crystal structure of (8S,9R,10S,11S,13S,14S,16S,17R)-9α-bromo-11-hydroxy-10,13,16-trimethyl-3-oxo-17-[2-(propionyloxy)acetyl]-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate monohydrate, C28H37BrO7·H2O, which has a 9α-Br atom in place of the 9α-Cl atom of monohydrated beclometasone dipropionate, one six-membered ring is planar (r.m.s. deviation = 0.02 Å) owing to its 1,4-diene-3-one composition, whereas the two other six-membered rings each have a chair conformation. The organic molecule and water molecules engage in hydrogen-bonding interactions, generating a helical chain running along the c axis of the orthorhombic unit cell.

17-Deoxoestrone [estra-1,3,5(10)-trien-3-ol]-methanol (3/1).

Three independent molecules of the title estrone derivative and a molecule of methanol comprise the asymmetric unit of the title compound [systematic name: 13-methyl-6,7,8,9,11,12,13,14,15,16-decahydrocyclopenta[a]phenanthren-3-ol–methanol (3/1)], 3C18H24O·CH3OH. Two of the estrone molecules exhibit 50:50 disorder (one displays whole-molecule disorder and the other partial disorder in the fused five- and six-membered rings) so that five (partial) molecular conformations are discernable. The conformation of the six-membered ring abutting the aromatic ring is close to a half-chair in all five components. The conformation of the six-membered ring fused to the five-membered ring is based on a chair with varying degrees of distortion ranging from minor to significant. Two distinct conformations are found for the five-membered ring: in four molecules, the five-membered ring is twisted about the bond linking it to the six-membered ring, and in the other, the five-membered ring is an envelope with the quaternary C atom being the flap atom. The crystal packing features O—H⋯O hydrogen bonding whereby the four molecules comprising the asymmetric unit are linked into a supramolecular chain along the b axis.