6945-01-3Relevant academic research and scientific papers
Aminothiazoles and aminothiadiazoles as nucleophiles in aminocarbonylation of iodobenzene derivatives
Gergely, Máté,Kollár, László
, p. 2030 - 2040 (2018/03/21)
Various 2-, 3- and 4-substituted iodobenzenes were aminocarbonylated using aminothiazole and aminothiadiazole derivatives in palladium-catalysed reaction. The reaction is chemospecific toward the corresponding carboxamides. Consequently, the application o
Design, synthesis and protection against pentylenetetrazole-induced seizure of N-aryl derivatives of the phthalimide pharmacophore
Davood, Asghar,Nematollahi, Alireza,Shafaroodi, Hamed,Shirazi, Mehrshad,Amini, Mohsen,Iman, Maryam
, p. 953 - 963,11 (2020/08/31)
A series of compounds including N-aryl substituents of phthalimide and 4-nitrophthalimide were synthesized and evaluated for their anticonvulsant properties. The in vivo screening data suggest that all the analogs have the ability to protect against pentylenetetrazole-induced seizures. These compounds exerted their maximal effects 30 min after administration. The most potent compound in both, tonic and clonic seizure was 1-naphthyl derivative (comp. 6), which was more active than the reference drug known as Phenytoin. Using an open pore model of the Na channel, these anticonvulsants were docked in the active site and examined in relation to the residues identified by mutagenesis as important for their binding energies. Docking studies revealed that all compounds (1-13) interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and additional hydrophobic interactions with domain I and II in the channel's inner pore.
Therapeutic effects of cantharidin analogues without bridging ether oxygen on human hepatocellular carcinoma cells
Yeh, Chao-Bin,Su, Chi-Jung,Hwang, Jin-Ming,Chou, Ming-Chih
experimental part, p. 3981 - 3985 (2010/09/11)
Previous research indicates that cantharidin, norcantharidin and their analogues exhibit anticancer activity due to their inhibition of cancer cell lines such as HL60, HT29 and L1210. The anticancer activities of cantharidin, norcantharidin and their analogues involve the suppression of serine/threonine protein phosphatases (PPs) activity. However, cantharidin is not suitable for cancer therapy because of its high cytotoxicity in vitro (IC50 = 21 μM in primary cultured rat hepatocytes). In this study, synthetic cantharidin analogues with a structure of aminothiazole compounds 3-9 and a structure of anhydride compounds 10-12 were screened for anticancer activities and cytotoxic effects on human hepatocellular carcinoma cell (HCC) lines HepG2, Sk-Hep1, and primary cultured rat hepatocytes. Experimental results indicated that compounds 3-9 did not perform as expected with regard to anticancer activity and exhibited lower cytotoxicity. Compound 10 promoted apoptosis in HepG2 (IC50 = 62 μM) and SK-Hep1(IC50 = 151 μM) cell lines. Compounds 11 and 12 had anticancer potential similar to that of compound 10. After treatment with compounds 3-12, primary cultured rat hepatocytes exhibited no cytotoxicity (IC50 > 200 μM). By investigating the structure-activity relationship (SAR) of these analogues as a whole, this study suggests that the anhydride ether oxygen such as in cantharidin, norcantharidin and compounds 10-12 may be correlated with HCC survival suppression. The results further suggest that the elimination of bridging ether oxygen on the ring, such as in compounds 10-12, can decrease cytotoxicity. Elimination of bridging ether oxygen on the ring, such as in compound 10, can decrease their cytotoxicity. Anhydride ether oxygen is crucial for inducing HCC cytotoxicity.
