Ahmed M. Sh. El-Sharief

Some reactions with Ketene dithioacetals: Part I: Synthesis of antimicrobial pyrazolo[1,5-a]pyrimidines via the reaction of ketene dithioacetals and 5-aminopyrazoles

Pyrazolo[1,5-a]pyrimidines were synthesized via the reaction of ketene dithioacetals and 5-aminopyrazoles. The antibacterial and antifungal activities of some selected compounds are also reported.

Synthesis and characterization of new types of halogenated and alkylated imidazolidineiminothiones and a comparative study of their antitumor, antibacterial, and antifungal activities

A series of twenty novel imidazolidineiminothiones (4-8) with various substituents at N-(1) and N-(3) were synthesized by various permutations of halogenated and alkylated N-arylcyanothioformanilides (1) with aromatic isocyanates (2). Preliminary screening of all compounds against Ehrlich ascites carcinoma cells (EAC) indicated that 5d, and 8a-c were the most active compounds as they displayed the highest percent inhibition of cell viability (80%, 70%, 80%, and 70%, respectively). Thus, they were further subjected to in vitro biological evaluation against other tumor cancer cell lines (HEPG2, HEP2, MCF7, HELA, and HCT116). The IC50 values ranged from 3.12 to 12.1 μg/mL where compound 8b (N-(1): 2,4-dimethoxyphenyl; N-(3): 4-methoxyphenyl) was markedly active against all cell lines and consistently produced low IC50 values in all cases (ranging from 3.12 to 4.34 μg/mL). This underscored the synergistic effect of the suitably positioned methoxy groups on the aromatic rings of N-(1) and N-(3) of the imidazolidineiminothiones. All compounds were also tested against microbial organisms (Escherichia coli, Sarcina lutea, Bacillus subtilis, and Staphylococcus aureus), and fungal strains (Candida albicans and Aspergillus flavus). Most tested compounds showed significant activities which could be optimized with the appropriate selection of matching aromatic substituents on N-(1) and N-(3).

Synthesis and Biological Evaluation of Bis‐Imidazolidineiminothiones: A Comparative Study

A series of 15 novel symmetrical and non‐symmetrical bis‐imidazolidineiminothiones (6a–g, 7a–e, 8a,b, and 9) with various substituents at N‐(1) (p‐tolyl, p‐methoxyphenyl, p‐ethoxyphenyl, p‐chlorophenyl, p‐bromophenyl, p‐iodophenyl, and 3,5‐dichlorophenyl) and different linkers between the N‐(3) atoms [4,4′‐oxybis(4,1‐phenylene), 2,2′‐dimethoxybiphenyl, and (1,3,3‐trimethylcyclohexyl)methyl)] were prepared in 65–75% yields from substituted N‐arylcyanothioformanilides and various bis‐isocyanates. Screening for cytotoxicity against the HEPG2, HEP2, MCF7, and HCT116 tumor cell lines gave IC50 values ranging from 6.3 to 84.6 µM, where compounds 6b,d,e,g and 7a were markedly active against a least one cell line, underlining the matching effect of properly positioned substituents on N‐(1) and the appropriate N‐(3)‐N‐(3) linker. Likewise, all heterocyles were tested against microbial organisms (Pseudomonas aeruginosa, Sarcina lutea, Bacillus pumilus, and Micrococcus luteus) and fungal strains (Candida albicans and Penicilium chrysogenum). Most compounds showed significant antibacterial and antifungal activities, reaching in certain cases the same level of antimicrobial activity as the standard antibacterial agent erythromycin and the antifungal agent metronidazole. The antimicrobial activity was further supported by quantitative assessment of susceptibilities of a selection of the preceding microorganisms using minimum inhibitory concentration and minimum bactericidal concentration techniques. Finally, the antiviral properties of all compounds were investigated against the viral strains HAV, HSV1, and CoxB4, where 6c,d,f and 7a,c,e were markedly active against one or two viral strains, reducing the virus plaque count of various viral strains by 66 to 88%. Structure activity relationship studies revealed several matching pairs of aromatic substituents on N‐(1) and the N‐(3)‐N‐(3) linkers, which could serve to optimize structural features for high activity to eventually render such compounds clinically useful drug agents.

Design, synthesis, antiproliferative activity, molecular docking and cell cycle analysis of some novel (morpholinosulfonyl) isatins with potential EGFR inhibitory activity.

New series of 5-(morpholinosulfonyl) isatin derivatives were designed and synthesized. The new compounds were characterized on the basis of spectral and elemental analyses. They were examined for their cytotoxic effects using SRB assay on four cancer cell lines HepG2, HCT116, CACO and MCF-7 in addition to the non-cancerous human cell line. They were non cytotoxic towards the normal derived cell line (IC50 value > 130 μM). Compounds 3, 6, 10 and 11 showed IC50 values less than 10 μM on three of the tested cell lines HepG2, HCT116 and CACO. Compounds 2h, 5, and 7b showed IC50 values less than or nearly equal 10 μM on HepG2, CACO and HCT116 respectively. Compounds 3 and 6 revelaed IC50 values less than 12 μM on MCF7. These obtained IC50 values are comparable with that of doxrubicin as it has showed IC50 range from 4.5 to 8.28 μM on the tested cell lines. All these promising derivatives showed inhibitory activity against EGFR with IC50 values less than 2 μM. The most potent EGFR inhibitors 7b (IC50 = 46 nM) and 10 (IC50 = 23 nM) showed to cause cell cycle arrest at G2/M phase and induce apoptosis. Molecular docking studies also were simulated to put insight and make better understanding to their structural features.