A comparative study of the behavior of cyanothioformamide and oxazolidine (thiones or iminothiones) towards some binucleophiles

Moussa

2013

Archiv der Pharmazie

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.

Section: Introductionmentioning

confidence: 99%

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

Moussa

2013

Archiv der Pharmazie

“…Therefore, all the reactions were performed for 60 min at 50 W and 80 °C, and the results are shown in Table 2. 35 [48]; 90 [33]; 92 [50]; 73 (82) [51]; 61 [49]; 75 (60) [52] 304 [48]; 90 [33]; 92 [50]; 73 (82) [51]; 61 [49]; 75 (60) [ min, and only in 22% after 60 min. In this manner, the synthesis of all other derivatives was performed at 80 °C and 1800 W for 60 min (Table 2).…”

Section: Resultsmentioning

confidence: 99%

Application of Deep Eutectic Solvents in the Synthesis of Substituted 2-Mercaptoquinazolin-4(3H)-Ones: A Comparison of Selected Green Chemistry Methods

et al. 2022

In this study, deep eutectic solvents (DESs) were used as green and eco-friendly media for the synthesis of substituted 2-mercaptoquinazolin-4(3H)-ones from different anthranilic acids and aliphatic or aromatic isothiocyanates. A model reaction on anthranilic acid and phenyl isothiocyanate was performed in 20 choline chloride-based DESs at 80 °C to find the best solvent. Based on the product yield, choline chloride:urea (1:2) DES was found to be the most effective, while DESs acted both as solvents and catalysts. Desired compounds were prepared with moderate to good yields using stirring, microwave-assisted, and ultrasound-assisted synthesis. Significantly, higher yields were obtained with mixing and ultrasonication (16–76%), while microwave-induced synthesis showed lower effectiveness (13–49%). The specific contribution of this research is the use of DESs in combination with the above-mentioned green techniques for the synthesis of a wide range of derivatives. The structures of the synthesized compounds were confirmed by 1H and 13C NMR spectroscopy.

“…[6][7][8][9][10][11][12] The classical methods for the synthesis of quinazolinedione ring system are the reaction of anthranilic acid and its derivatives with isothiocyanates or their equivalents. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Recently, our research group was involved in the synthesis and determination of the anti-proliferative and anti-inflammatory activity of a large number of heterocyclic compounds. 28,29 In the continuation of this pro-gram, in this context, we aimed to develop an efficient and facile approach to synthesize and measure the cytotoxicity of a series of thioxoquinazolin-4(1H)-ones from anthranilic acid and ethoxycarbonylisothiocyanate.…”

Section: Introductionmentioning

confidence: 99%

Uses of Anthranilic Acid for the Synthesis of Dihydroquinazolin Derivatives with Antitumor, Antiproliferative and Pim-1 kinase Activities

Mohareb

Halim

2018

ACSi

The reaction of anthranilic acid with ethoxycarbonylisothiocyanate gave the ethyl 4-oxo-2-thioxo-1,2-dihydroquinazoline-3(4H)-carboxylate (4). The reaction of compound 4 with hydrazine hydrate and α-halocarbonyl derivatives was found to give either hydrazono or S-alkylated products. Heterocyclization reactions of some of the S-alkylated derivatives 8 and 12 were carried out to afford thiazole, pyran and pyridine derivatives. The cytotoxicity of the newly synthesized compounds towards the six cancer cell lines NUGC, DLD-1, HA22T, HEPG-2, HONE-1 and MCF-7 showed that compounds 6, 8, 13, 19c-f, 21b-f, 24a and 24c with the highest cytotoxicity. The c-Met kinase inhibition for some of the selected compounds showed that compounds 8, 13, 19d, 21e, 21f and 24a were the most active compounds. Screening toward tyrosine kinases revealed that compounds 13, 21e and 24a exhibit the highest inhibitions and therefore their molecular modeling was described. In addition, compounds 13 and 24a showed the highest activities towards Pim-1 kinase.