Synthesis and Evaluation of 5-imino-4-thioxoimidazolidin-2-one Derivatives as Antibacterial and Antifungal Agents.

OBJECTIVE: It was interesting to synthesize some new 5-imino-4-thioxoimidazolidin-2- one derivatives with different halogenated and alkylated aromatic substituents at N-(1) and N-(3) and evaluation of their expected antibacterial and antifungal activities. METHODS: New 5-imino-4-thioxoimidazolidin-2-one derivatives were synthesized through the reaction of different halogenated and alkylated N-arylcyanothioformamides with halogenated and alkylated aryl isocyanates. RESULTS: 5-Imino-4-thioxoimidazolidin-2-ones were obtained in high yields with excellent purity. The activities of imidazolidines as antibacterial and antifungal agents were studied. Some of the imidazolidine derivatives displayed significant antibacterial and antifungal activities. CONCLUSION: 5-Imino-4-thioxoimidazolidin-2-ones were obtained in 77-90% yields with excellent purity. The antibacterial and antifungal activities suggest that some of the imidazole derivatives possess significant antimicrobial activity against B. subtilis, K. pneumonia and C. albicans and moderate activity against S. aureus.

Synthesis and anticancer activity of thiourea derivatives bearing a benzodioxole moiety with EGFR inhibitory activity, apoptosis assay and molecular docking study.

New thiourea derivatives bearing a benzodioxole moiety were synthesized via the reaction of 5-isothiocyanatobenzodioxole with amino compounds such as aromatic amines, sulfa drugs, heterocyclic amines, hydrazines and hydrazides. The anticancer activity of the synthesized thiourea derivatives was examined against HCT116, HepG2 and MCF-7 cancer cell lines. Most of thiourea derivatives revealed significant cytotoxic effect, in some cases greater than the doxorubicin. As example, IC50 values of N1,N3-disubstituted-thiosemicarbazone 7 were 1.11, 1.74 and 7.0 µM for HCT116, HepG2 and MCF7, respectively; IC50 values of doxorubicin were 8.29, 7.46 and 4.56 µM, respectively. The anticancer mechanisms were studied via EGFR inhibition and apoptosis assessments, as well as molecular docking.

Development of a Novel Series of Anticancer and Antidiabetic: Spirothiazolidines Analogs.

4-(4-Aminophenyl)-1-thia-4-azaspiro[4.5]decan-3-one 1 was prepared and allowed to react with nitrogen nucleophiles to give the corresponding hydrazones 2-4. Further, compound 1 underwent diazotization and afforded the parallel hydrazono derivative 5; moreover, compound 1 refluxed with active methylene derivatives yielded the corresponding aminospirothiazolo pyridine-carbonitrile derivative 6 and spirothiazolopyridinone-carbonitrile derivative 7. Condensation of spirothiazolidine 1 with 4-chlorobenzaldehyde gave the corresponding spiro arylidiene derivative 8, which was utilized as a component of Micheal addition to react with excess of nitrogen nucleophiles to yield novel ring frameworks 4-(3'-(4-chlorophenyl)-spiro [cyclohexane-1,5'-pyrazolo[3,4-d]thiazol]-6'(1'H)-yl)aniline (9) and 4-(3'-(4-chlorophenyl)-6'H- spiro[cyclohexane-1,5'-thiazolo[5,4-d]isoxazol]-6'-yl)aniline (10). Finally, when spirothiazolo pyridinone-carbonitrile derivative 7 sodium salt generated in situ was reacted with different alkyl halides, it produced the corresponding N-derivatives 12-16. Three compounds, 6, 14, and 16, showed high significantly anticancer activities compared with Doxorubicin® (positive control) against human breast carcinoma (MCF-7) and human liver carcinoma (HepG-2) cell lines. On the other hand, compounds 6 and 9 showed higher therapeutic indices for both of alpha-amylase inhibitor and alpha-glucosidase inhibitor than the other tested compounds compared with the antidiabetic Acarbose (positive control).

Synthesis and anticancer activity of bis-benzo[d][1,3]dioxol-5-yl thiourea derivatives with molecular docking study.

New thiourea derivatives incorporating two benzo[d][1,3]dioxol-5-yl moieties have been synthesized through the reaction of two molecules of benzo[d][1,3]dioxol-5-yl isothiocyanate with one molecule of various diamino derivatives. The synthesized compounds were examined for their cytotoxic effects using SRB assay on three cancer cell lines HepG2, HCT116 and MCF-7. Most of compounds showed significant antitumor activity and some compounds showed strong results greater than the reference drug. As example, IC50 values of 1,1'-(1,4-phenylene)bis(3-(benzo[d][1,3]dioxol-5-yl)thiourea) 5 were 2.38 µM for HepG2, 1.54 µM for HCT116 and 4.52 µM for MCF7, while the IC50 values of standard drug doxorubicin were 7.46, 8.29 and 4.56 µM, respectively. Interestingly, these compounds were non cytotoxic toward the tested normal cell line (IC50 value > 150 µM). The anticancer mechanisms were studied via EGFR inhibition assessment, annexin V-FITC apoptosis assessment, cell cycle analysis and study the effect on mitochondrial apoptosis pathway proteins Bax and Bcl-2 as well as molecular docking studies.

Synthesis and antiviral evaluation of alpha-amino acid esters bearing N6-benzyladenine side chain.

A series of peptide derivatives conjugated with a purine residue were synthesized. The prepared compounds were tested for antiviral activity against Hepatitis B Virus (HBV) displaying different degrees of antiviral activities or inhibitory actions.