Wasfi A. Al-Masoudi

Thiosugar Nucleosides. Synthesis and Biological Activity of 1,3,4‐Thiadiazole, Thiazoline and Thiourea Derivatives of 5‐Thio‐d‐Glucose

New acylated 5‐thio‐β‐d‐glucopyranosylimino‐disusbstituted 1,3,4‐thiadiazols 8, and 11 were prepared, via spontaneous rearrangements, by cycloaddition of the glycosyl isothiocyanate 2 with the reactive intermediates 1‐aza‐2‐azoniaallene hexachloroantimonates 4 and 6, respectively. Reaction of 2 with aminoacetone or chloroethylamine afforded the acylated 5‐thio‐β‐d‐glucopyranosyl‐4‐imidazoline‐2‐thione nucleoside 16 and glucopyranosylamino‐2‐thiazoline derivative 18, respectively. Deblocking of 8, 11, 17 and 19 furnished the free nucleoside analogues 9, 12, 18 and 20, respectively. Analogously, treatment of 2 with chloroethylamine in the 1:2 ratio afforded the thioureylendisaccharide 21. No in vitro antiviral activity against HIV‐1, HIV‐2, human cytomegallovirus (HMCV), has been found for the new synthesized compounds.

Synthesis of some novel acyclolumazine N-1 nucleosides

Abstract Reactjon of (2-acetoxyethoxy)methyl bromide with the silylated lumazine bases (1-6) in the presence of n-Bu4NI leads to the formation of the nucleosides 8, 10, 12, 14, 16 and 18 respectively. Deacetylation with methanolic ammonia afforded the free nucleosides 9, 11, 13, 15, 17 and 19, respectively, in good yields. Structural proofs of the newly synthesized compounds are based on elemental analyses, UV and 1H-NMR spactra. None of the acyclic nucleosides exhibited antiviral activity against HSV-1 in vitro.

Synthesis, crystal structure, anti-HIV, and antiproliferative activity of new oxadiazole and thiazole analogs

A series of 2-adamantyl-5-arylthiazolyl-1,3,4-oxadiazoles 7a–x together with thiazoles 13 and 14 were synthesized. Compounds 7a–l, 13, and 14 were tested in vitro with the aim of identifying novel lead compounds active against human immunodeficiency virus type-1 and human immunodeficiency virus type-2 activity in MT-4 cells. Title compounds were also tested against representatives of Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Salmonella spp.), various mycobacterial strains (Mycobacterium fortuitum and Mycobacterium smegmatis), yeast (Candida albicans), and mold (Aspergillus fumigatus). None of the compounds showed antiviral or antimicrobial activity, except compounds 13 and 14 exhibited anti-human immunodeficiency virus-1 activity with EC50 values of 1.79 and 2.39 μM with Selectivity index = 18 and 4, respectively. On the other hand, compounds 7a and 7j showed a marked cytotoxicity against the human CD4+ lymphocytes (MT-4). Therefore, 7a and 7j were evaluated for their antiproliferative activity against two solid tumor-derived cell lines, which exhibited IC50 values of 8.1 ± 0.10 µM and 4.8 ± 0.08 µM against Hep-G2 cell lines, respectively.

Potassium Tellurocyanate Mediated Coupling Reactions of N-(1-Chloroethylidene)Arylamines

Abstract The reaction of potassium tellurocyanate (prepared in situ) with N-(1-chloroethylidene)arylamines (i.e., 4-RC6H4N = C(CH3)Cl, where R = H, Cl, CH3 and NO2) in DMSO solution gave unexpectedly, after hydrolysis, the corresponding N-(3-(arylamino)butan-2-ylidene)arylamines in 63–78%. Reaction of N-(3-(arylamino)butan-2-ylidene)arylamines with SOCl2 or with Br2 resulted in the substitution of a halogen on the aromatic rings. The presence of a water molecule within the structure of the synthesized diimines was rationalized theoretically by Density Functional Theory (DFT). All compounds were characterized by elemental analysis, IR, NMR and mass spectroscopic data. GRAPHICAL ABSTRACT

Synthesis, X-ray structure, in vitro HIV and kinesin Eg5 inhibition activities of new arene ruthenium complexes of pyrimidine analogs

Abstract Three new ruthenium(II)-arene complexes of the general formula [{(η6-p-cymene)Ru(L)}2](Cl)2), where L are monastrol (L1), ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-pyrimidine-5-carboxylate (L2) or its 4-bromophenyl analog (L3), have been synthesized and characterized by elemental analysis, 1H, 13C, and 2-D NMR spectroscopy. The X-ray diffraction study of complex 1 showed the presence of a dicationic diruthenium complex where two thioxopyrimidines act as tridentate μ,κN:κ2S ligand, bridging two Ru ions through the pyrimidine nitrogen and sulfur atoms. All new complexes were evaluated in vitro for their antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells using MTT assay. Additionally, complexes 1–3 were screened for their inhibitory activity against the ATPase enzyme and the motor-protein Kinesin Eg5. Complex 1 was found to inhibit microtubule-stimulated ATPase activity of kinesin of IC50 = 30 μM (monastrol, IC50 = 10 μM).

Amino acid derivatives. Part 6. Synthesis, in vitro antiviral activity and molecular docking study of new N -α-amino acid derivatives conjugated spacer phthalimide backbone

A series of phthalimido-(substituted-alkyl-2-thioureido)alkyl carboxylic acid derivatives 5–13 and methyl 2-(4-(phthalimido-2-yl)butanamido)alkyl carboxylates 14–23 were synthesized with the aim to develop newly non-nucleoside reverse transcriptase inhibitors (NNRTIs). The new synthesized compounds were assayed against human immunodeficiency virus-1 and human immunodeficiency virus-2 in MT-4 cells. The results showed that 22 and 23 were the only compounds in the series inhibiting human immunodeficiency virus-1 (IIIB strain) replication in cell culture with an EC50 value of >2.07 and >4.23 μM (SI = 7 and 5), respectively. In addition, the new analogs were screened against hepatitis virus C genotype 1b in the Huh-5-2 replicon system. Compounds 9 and 12 were the most active analogs of the series and exhibited activity with EC50 = 26.7 and 22.0 μM (SI > 1.87 and >2.28, respectively). The molecular docking of 22 with some amino acids of human immunodeficiency virus reverse transcriptase has been studied.

Spectroscopic Study of some Schiff Bases Derived from Dibenzoylmethane

A series of Schiff bases 7-11 derived from dibenzoylmethane have been prepared. The UV, IR, 1 H NMR and mass spectra revealed theses compounds were existed mainly as the keto-enamine tautomer in the solution. The absorption bands which appeared in the range λmax = 376-406 nm were assigned to the electronic transitions which arised from the central hydrogen bonded chelated unsaturated ring system in this tautomer. The appearance of the broad singlet near  = 13 ppm due to the N-H proton and a singlet near  = 6 ppm due to the –C=C-H proton inaddition to benzoyl fragment ion signal m/z = 105 in the mass spectra supported the above suggested products.