Ahmed M. Zaghloul

Chemical Constituents of the Essential Oils of Origanum syriacum and Stachys aegyptiaca

AbstractThe Essential Leaf Oils Of Origanum Syriacum Var. Aegyptiacum and Stachys Aegyptiaca (Lamiaceae), Were Prepared By Hydrodistillation and Studied By Cgc and Gc-Ms. Among The 28 Compounds Identified In The Oil Of Origanum, Up To 83% Consists Of The Antiseptic and Flavoring Agent Carvacrol. In Addition, Carvacrol Methyl Ether and Carvacryl Acetate Are Present In Minute Amounts. The Monoterpene Hydrocarbon Fraction Accounts For Nearly 12% Of The Oil Of Which P-Cymene, γ-Terpinene, Myrceneand A-Thujene Are The Major Components. The Sesquiterpene Compounds and The Monoterpene Alcohols Occur In Rather Insignificant Concentrations.The Oil Of Stachys Aegyptiaca Consists Mainly Of 14 Monoterpene Hydrocarbons (75%), 4 Oxygenated Monoterpenes (1.1%) and 7 Sesquiterpene Hydrocarbons (17%). The Dominant Compound Is Ot-Pinene.

Rational Design and Semisynthesis of Betulinic Acid Analogues as Potent Topoisomerase Inhibitors

Chemical transformation studies were conducted on betulinic acid (1), a common plant-derived lupane-type triterpene. Eleven new rationally designed derivatives of 1 (2-5 and 7-13) were synthesized based on docking studies and tested for their topoisomerase I and IIalpha inhibitory activity. Semisynthetic reactions targeted C-3, C-20, and C-28 in 1. Structures of the new compounds were confirmed by spectroscopic methods (1D and 2D NMR and MS). Compound 9, 3-O-[N-(phenylsulfonyl)carbamoyl-17beta-N-(phenylsulfonyl)amide]betulinic acid, showed 1.5-fold the activity of CPT in a topoisomerase I DNA relaxation assay. Four out of 14 betulinic acid analogues (5, 9, 11, and 12) showed 1.5-fold the activity of etoposide in a topoisomerase II assay. The new analogues exhibited better cytotoxic activities against the human colon cancer cells SW948 and HCT-116 and the breast cancer cell line MDA-MB-231 compared to the parent (1). Betulinic acid (1) is a potential scaffold for the design of new topoisomerase I and IIalpha inhibitors.

Design and pharmacophore modeling of biaryl methyl eugenol analogs as breast cancer invasion inhibitors

Cell invasion and migration are required for the parent solid tumor cells to metastasize to distant organs. Microtubules form a polarized network, enabling organelle and protein movement throughout the cell. Cytoskeletal elements coordinately regulate cells motility, adhesion, migration, exocytosis, endocytosis, and division. Thus, microtubule disruption can be a useful target to control cancer cell invasion and metastasis. The phenolic ether methyl eugenol (1), the major component of the essential oil of the leaves of Melaleuca ericifolia Sm. (Myrtaceae), was used as a starting scaffold to design eleven new and three known anti-tubulin agents 2-15 using carbon-carbon coupling reactions. A computer-assisted approach was used to design these new biaryl derivatives using colchicine-binding site of tubulin as the molecular target and colchicine as an active ligand. Several derivatives showed potent inhibitory activity against MDA-MB-231 cell migration at the 1-4microM dose range. The Z isomers, 4 and 15 were more active as invasion inhibitors compared to their structurally related E isomers, 2 and 14. The cytotoxic activities of compounds 2-15 against two breast cancer cell lines MDA-MB-231 and MCF-7 were evaluated. Anti-invasive activity of the semisynthetic derivatives is not due to a direct cytotoxic effect on MDA-MB-231. Analogs 2-15 may promote their anti-invasive activity through the induction of changes in cell morphology. A pharmacophore model was generated involving seven essential features for activity, which was consistent with a previously generated colchicine site inhibitors model.

Antiproliferative Triterpenes from Melaleuca ericifolia

Three new 28-norlupane triterpenes, 28-norlup-20(29)-en-3beta-hydroxy-17beta-hydroperoxide (1), 28-norlup-20(29)-en-3beta-hydroxy-17alpha-hydroperoxide (2), and 20 S-17beta,29-epoxy-28-norlupan-3beta-ol (3), were isolated from the leaves of Melaleuca ericifolia along with eight known pentacyclic triterpenes. The structures of the new compounds were elucidated by spectroscopic methods including 1D and 2D NMR spectroscopy and mass spectrometry. The isolated triterpenes were evaluated for antiproliferative activity against the malignant +SA mammary epithelial cell line.

Pregnane glycosides from Stapelia variegata.

Eleven new pregnane ester glycosides have been isolated from the aerial parts of Stapelia variegata. Eight of the recognized compounds were established to possess the same trioside moiety, viz. 3-O-[3-O-methyl-6-deoxy-beta-D-allopyranosyl-(1-4)-beta-D- cymaropyranosyl-(1-4)-beta-D-cymaropyranoside]. These compounds were identified as: stavaroside A: 12-O-beta-angeloyl-20-O-benzoyl sarcostin; stavaroside B: 12-O-beta-angeloyl-20-O-tigloyl sarcostin; stavaroside C: 11 alpha-acetoxy 2 beta-benzoxy-3 beta,8 beta, 14 beta-trihydroxy-pregn-5-ene-20-one; stavaroside D: 11 alpha-acetoxy- 12 beta-tigloxy-3 beta,8 beta,14 beta-trihydroxy-pregn-5-ene-20-one; stavaroside E: 12-O-beta-benzoyl sarcostin; stavaroside F: 11 alpha-acetoxy-12 beta-acetoxy-3 beta,8 beta,14 beta-trihydroxy-pregn-5- ene-20-one; stavaroside G: 12-O-beta,20-O-diacetyl sarcostin and stavaroside H: 3 beta, 8 beta, 11 alpha, 12 beta, 14 beta-pentahydroxy-pregn-5- ene-20-one. The other three compounds were shown to possess the same tetraside sugar moiety, viz. 3-O-[beta-D-glucopyranosyl- (1-4)-3-O-methyl-6-deoxy-beta-D-allopyranosyl-(1-4)-beta-D-cymaropyra nosyl- (1-4)-beta-D-cymaropyranoside]. These compounds were identified as: stavaroside I: 1 alpha, 12 beta-angeloxy and benzoxy-3 beta,8 beta,14 beta-trihydroxy- pregn-5-ene-20-one; stavaroside J: 11 alpha-acetoxy-12 beta-benzoxy-3 beta, 8 beta,14 beta-trihydroxy-pregn-5-ene-20-one and stavaroside K: 11 alpha-acetoxy-12 beta-tigloxy-3 beta,8 beta,14 beta-trihydroxy-pregn-5-ene- 20-one. The structural elucidation of the isolated compounds was aided significantly on the basis of the chemical and spectral evidence. The decisive assignments of the ester positions were based on the Inverse Detected-Heteronuclear Multiple Bond Connectivity (HMBC) experiments.

Transformation of jervine by Cunninghamella elegans ATCC 9245

Preparative-scale fermentation of the known C-nor-D-homosteroidal jerveratrum alkaloid jervine with Cunninghamella elegans (ATCC 9245) has resulted in the isolation of (-)-jervinone as the major metabolite. In addition, C. elegans ATCC 9245 was able to epimerize C-3 of jervine, producing 3-epi-jervine. This epimerization reaction was similar to that reported for tomatidine, the known spirosolane-type Solanum alkaloid. The structure elucidation of both metabolites was based primarily on 1D- and 2D-NMR analyses.

A further guaianolide from Arctotis grandis.

Abstract Two further guaianolides were isolated from the aerial parts of Arctotis grandis .

Taxodione, a DNA-Binding Compound from Taxodium distichum L. (Rich.)

8-β-Hydroxypimar-15-en-19-oic acid (1), taxodione (2), 6,7-dehydro-8-hydrotaxodone (3), quercetin-3-O-β-d-glucopyranoside (4), and shikimic acid (5) were isolated from the leaves of Taxodium distichum L. (Rich.) for the first time. Previously reported compounds [β-sitosterol (6), isorhamnetin (7), quercetin (8), isorhamnetin-3-O-α-arabinofuranoside (9), quercetin- 3-O-α-arabinofuranoside (10)] have also been isolated. The activity of taxodione as an inhibitor for hepatic stellate cells was determined. The antitumour activity of 2, 3, and 5 using a DNA affinity probe was examined.

Two steroidal alkaloids from veratrum viride

Abstract A phytochemical study of the roots and rhizomes of Veratrum viride led to the isolation of the two new steroidal alkaloids, rubivirine, identified as 12β-hydroxyisorubijervine, and veramivirine, identified as 12β-hydroxyveramiline. Structural elucidation of the two compounds was aided by 2D-NMR spectral analyses.

BIOTRANSFORMATION OF α-SANTONIN

AbstractBacillus cereus UI-1477 was able to convert α-santonin into one major metabolite with a 64% yield. The structure of the obtained metabolite was suggested with 1D and 2D 1H-, 13C-NMR as 1,2-dihydrosantonin. Biological evaluation showed a complete loss of both anthelmintic and antimicrobial activity of 1,2-dihydrosantonin in comparison to α-santonin.