- Synthesis, antimicrobial, anti-cancer and in silico studies of new urea derivatives
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The reaction of an alkyl or aryl isocyanates with some primary amines in acetonitrile at room temperature afforded the corresponding alkyl- and aryl-urea derivatives. All the prepared urea compounds have been elucidated by FTIR, NMR, and elemental analysis. The compounds 1 and 3 were confirmed by single-crystal X-ray diffraction. The 4-tolylsulfonyl isocyanate reacted with the aryl amines 1, 2, 3, and 2,4-dichloroaniline to afford the corresponding sulfonylurea derivatives 5–8. Likewise, the reaction of the isocyanates with 2,4-dichloroaniline, 5-methyl isoxazole-3-amine, and 2-aminothiazole derivatives gave the corresponding urea derivatives 9–17. All the prepared compounds 5–17 were tested in vitro as anti-microbial and anti-HepG2 agents. Moreover, analyzing gene expression of TP53-exon4 and TP53-exon7, DNA damage values, and DNA fragmentation percentages have been discussed. The compounds 5 and 8 recorded the highest activity against the tested microbial strains with maximum activity against C. albicans (50 mm) and B. mycoides (40 mm), respectively. The compounds 5 inhibited the growth of E. coli, S. aureus, and C. Albicans at the MIC level of 0.0489 μM, while the compound 8 was able to inhibit the visible growth of E. coli and C. albicans at MIC value of 3.13 μM and S. aureus at 0.3912 μM. In the same line, compound 5 showed the best cytotoxic activity against the HepG2 cell line (IC50 = 4.25 μM) compared to 5 fluorouracil with IC50 = 316.25 μM. Expression analysis of liver cancer related to a gene including TP53-exon4 and TP53-exon7 was used in HepG2 Liver cancer cell lines using RT-qPCR. The expression values of TP53-exon4 and TP53-exon7 genes were decreased. The DNA damage values and DNA fragmentation percentages were increased significantly (P 0.01) in the treated HepG2 (5) sample compared with the negative control. Docking studies were performed for the synthetic compounds against 2 bacterial proteins (DNA gyrase subunit B, and penicillin binding protein 1a) that are known targets for some antibiotics, and one cell division protein kinase 2 (CDK2) as target for anticancer drugs.
- Sroor, Farid M.,Othman, Abdelmageed M.,Tantawy, Mohamed A.,Mahrous, Karima F.,El-Naggar, Mostafa E.
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- Method for synthesizing sulphaguanidine
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The invention discloses a method for synthesizing sulphaguanidine. According to the method, sulfonamide and guanidine hydrochloride are used as raw materials and are catalyzed by iodide to synthesize sulphaguanidine in one step. The method has the advantages of short process route and little environment pollution.
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Paragraph 0017; 0018
(2016/10/31)
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- Synthetic method for sulfadiazine
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The invention discloses a synthetic method for sulfadiazine. The sulfadiazine is synthesized with sulphaguanidine and malonaldehyde as raw materials. The synthetic method has the advantages of being mild in reaction condition, short in reaction time, high in conversion rate and beneficial to industrial production.
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Paragraph 0015-0016
(2017/01/26)
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- Synthesis and acrosin inhibitory activity of substituted 4-amino-N-(diaminomethylene) benzenesulfonamide derivatives
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A series of new substituted 4-amino-N-(diaminomethylene) benzenesulfonamides were synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds showed potent acrosin inhibitory activities with compounds 4o and 4p being significantly more potent than the control compound N-alpha-tosyl-l-lysyl-chloromethyl-ketone (TLCK). The compounds provide a new scaffold for the development of acrosin inhibitory agents.
- Ding, Lili,Zhu, Ju,Zheng, Canhui,Sheng, Chunquan,Qi, Jingjing,Liu, Xuefei,Han, Guangqian,Zhao, Juntao,Lv, Jiaguo,Zhou, Youjun
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supporting information; scheme or table
p. 6674 - 6677
(2011/12/04)
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- Novel method for synthesis of sulphaguanidine
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The microwave-enhanced synthesis of sulphaguanidine is achieved rapidly and in good yield via the step-wise reaction of cyanamide with sulphonamide in the presence of acidic alumina or montmorillonite clays (KSF and K10).
- Singh, Vikram,Kaushik
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experimental part
p. 645 - 648
(2012/05/04)
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- Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors
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Screening of the NCI Diversity Set-1 identified PI-083 (NSC-45382) a proteasome inhibitor selective for cancer over normal cells. Focused libraries of novel compounds based on PI-083 chloronaphthoquinone and sulfonamide moieties were synthesized to gain a better understanding of the structure-activity relationship responsible for chymotrypsin-like proteasome inhibitory activity. This led to the demonstration that the chloronaphthoquinone and the sulfonamide moieties are critical for inhibitory activity. The pyridyl group in PI-083 can be replaced with other heterocyclic groups without significant loss of activity. Molecular modeling studies were also performed to explore the detailed interactions of PI-083 and its derivatives with the β5 and β6 subunits of the 20S proteasome. The refined model showed an H-bond interaction between the Asp-114 and the sulfonamide moiety of the PI-083 in the β6 subunit.
- Lawrence, Harshani R.,Kazi, Aslamuzzaman,Luo, Yunting,Kendig, Robert,Ge, Yiyu,Jain, Sanjula,Daniel, Kenyon,Santiago, Daniel,Guida, Wayne C.,Sebti, Said M.
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experimental part
p. 5576 - 5592
(2010/09/15)
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- Protease inhibitors: Synthesis and QSAR study of novel classes of nonbasic thrombin inhibitors incorporating sulfonylguanidine and O- methylsulfonylisourea moieties at P1
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Using benzamidine as a lead molecule, two series of alkyl/aralkyl/arylsulfonylguanidines/sulfonyl-O-methylisoureas have been prepared and assayed as inhibitors of two serine proteases, thrombin and trypsin. The study showed that sulfaguanidine and its corresponding O- methylisourea derivative possess moderate but intrinsically selective thrombin inhibitory properties, with K(I)'s around 100 nM against thrombin and 1350-1500 nM against trypsin. Further elaboration of these two molecules afforded compounds that inhibited thrombin with K(I)'s in the range of 12-50 nM, whereas affinity for trypsin remained relatively low. Such compounds were obtained by attaching benzyloxycarbonyl- or 4-toluenesulfonylureido-protected amino acids (such as L- and D-Phe or L-Pro) or dipeptides (such as Phe-Pro, Gly-His, β-Ala-His, or Pro-Gly) to the two leads mentioned above, sulfaguanidine and 4-aminobenzenesulfonyl-O-methylisourea. Thus, the present study proposes two novel approaches for the preparation of high-affinity, specific thrombin inhibitors: two novel S1 anchoring moieties in the already large family of arginine/amidine-based inhibitors and novel peptidomimetic scaffolds obtained by incorporating tosylureido amino acids in the hydrophobic binding site(s). The first one is important for obtaining bioavailable thrombin inhibitors, devoid of the high basicity of the commonly used arginine/amidine-based inhibitors, whereas the second one may lead to improved water solubility of such compounds due to facilitated metal (sodium) salts formation (at the relatively acidic SO2NHCO protons) as well as increased stability at hydrolysis (in vivo). A QSAR study also explained the activity in terms of global properties of the molecules, electronic properties of the sulfonylguanidine/sulfonylisourea moiety, and novel descriptors, the frontier orbital phase angles (FOPA), that account for the directions of the nodes in the π orbitals in the aromatic portion of those of the drugs in which the sulfonyl group was bound to a benzene ring. For thrombin inhibition, the size of the molecule was the dominant influence, while for trypsin inhibition the FOPA was the principal determinant of activity. The dependence of activity on the FOPA variables is perhaps the clearest example of a quantum effect in pharmacology and suggests a promising new tool for drug design.
- Supuran, Claudiu T.,Scozzafava, Andrea,Briganti, Fabrizio,Clare, Brian W.
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p. 1793 - 1806
(2007/10/03)
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- Process for formulating a synthetic drug for use in animal feed, and resulting formulation
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A method of formulating a synthetic drug for use in animal feed, for the purpose of reducing carry-over of the synthetic drug to subsequent lots of animal feed in the feed mill.
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