Synthesis and Characterization of Macrocyclic Chiral Tröger's Base Phenhomazine Candidates as Anticancer Agent.

1,4,7,10-Tetraoxa[10](2,8)trögerophane 5 was synthesized from its corresponding precursors. Heating of 2 with p-nitrophenoxide afforded bis(p-nitrophenyl)ether 3, which was treated with hydrazine hydrate to give bis(p-aminophenyl)ether 4. Treatment of 4 with paraformaldehyde and triflouroacetic anhydride gave trögerophane 5. Reaction of 5 with trifluroacetic anhydride afforded phenhomazine derivative 6, which was treated with potassium carbonate to afford tetrahydrophenhomazine 7. Finally, reaction of 7 with phenacylchloride, bromoacetic acid, or ethyl bromoacetate in the presence of triethyl amine under reflux, afforded the corresponding macrocyclic compounds 8, 9 and 10, respectively. The synthesized trögerophane,precursors and its newly synthesized phenhomazines derivatives were screened for anticancer activity. Results revealed that 1,4,7,10-tetraoxa[10](2,8)trögerophane had a promising selectivity towards colon cancer cell line with an IC50 of 92.7 µg/ml.

Synthesis and Molecular Docking of New Thiophene Derivatives as Lactate Dehydrogenase-A Inhibitors.

BACKGROUND & OBJECTIVE: A series of novel derivatives possessing the thiophene moiety were synthesized using ethyl 5'-amino-2,3'-bithiophene-4'-carboxylate as the starting material. METHODS: The new synthesized derivatives were screened as lactate dehydrogenase (LDH) inhibitors. LDH plays an important role in glucose metabolism in cancer cells and can affect tumor genesis and metastasis. RESULTS: 3-Substituted p-tolylthieno[2,3-d]pyrimidin-4(3H)-ones 4 were the most potent inhibitors in this study compared to Galloflavin reference drug. CONCLUSION: Molecular docking studies on the Human Lactate Dehydrogenase active site were carried out on the synthesized compounds and the MolDock scores ranged between -127 to -171.

Design, Synthesis and In-vivo Anti-inflammatory Activity of New Celecoxib Analogues as NSAID.

BACKGROUND: A new series of Celecoxib analogues were easily synthesized via reactions of 4-(2-(1-chloro-2-oxopropylidene)hydrazinyl)benzene sulfonamide (1) with active methylene compounds and dialkyl malonate. In addition, compound 1 was reacted also with thiourea derivatives and thiosemicarbazone derivatives to afford thiazole derivatives 9 and 11, respectively. Furthermore, triazolo pyrimidine derivatives 13 were prepared via reaction of compound 1 with pyrimidine thione derivatives. The structures of the new synthesized compounds were assigned by elemental analysis and spectroscopic data. The new analogues were screened for their in vivo anti-inflammatory activity using carrageenan-induced paw edema method. CONCLUSION: They showed moderate to good in vivo anti-inflammatory effects. Compounds 1, 6 and 11b were the most active compounds that reduced the paw edema induced by carrageenan by 12.25 %, 12.96 % and 12.97% respectively, as compared to the Indomethacin that inhibited the oedema volume by 7.47 %.