103-04-8Relevant academic research and scientific papers
The synthesis and characterization of tetramic acid derivatives as Mdm2-p53 inhibitors
Muszak, Damian,?abuzek, Beata,Brela, Mateusz Z.,Twarda-Clapa, Aleksandra,Czub, Miroslawa,Musielak, Bogdan,Surmiak, Ewa,Holak, Tad A.
, p. 161 - 174 (2019)
We present syntheses, prediction of tautomer forms and activities of the second generation of the Mdm2-p53 inhibitors that are based on the tetramic acid scaffold. The inhibitors do not contain 6-chloroindole. Binding of these compounds to Mdm2 was checked by two orthogonal methods: the fluorescence polarization and the 1H-15N HSQC NMR titration experiments. We discovered that the 3-phenylthio-substituted tetramic acid derivatives exist in solution solely in their enol forms which is in contrast to the similar 3-aliphatic substituted derivatives. The inhibitory (Ki) and dissociation (KD) constants are in low micromolar ranges with the best binding compound 9a having KD = 2.9 μM. Furthermore, our data show that the compounds indeed bind to the p53-binding pocket of Mdm2 and do not cause dimerization of Mdm2. The current work provides solid base for further rational design of the Mdm2/p53 inhibitors.
HEXANE-SOLUBLE COMPLEXES OF ALKYL- AND ALKENYL-SODIUM COMPOUNDS WITH MAGNESIUM ALKOXIDES
Screttas, Constantinos G.,Micha-Screttas, Maria
, p. 1 - 12 (1986)
Unsolvated alkylsodium compounds are solubilized in hexane or methylcyclohexane by complexation with magnesium 2-ethoxyethoxide.The soluble species appear to have well defined stoichiometries, characterized by the Na/Mg ratio.Thus butylsodium forms 2/1 complex which is of moderate thermal stability, but if sufficient magnesium alkoxide is added to the 2/1 complex to make the Na/Mg ratio 1/1, than the complex becomes thermally very stable.Both of the BuNa complexes exhibit normal organometallic reactivity toward CO2, but with benzophenone the main product is the reduction rather than the addition product.The pronounced reducing ability is also manifested by the reduction of transition metal salts to either the matallic state (e.g.AgNO3, CoCl2) or to a lower valency state (e.g.TiCl4).The BuNa complexes react very rapidly with potassium metal and undergo sodium metal displacement. Alkenylsodiums derived by metalation of olefins may also form soluble complexes with magnesium 2-ethoxyethoxide.
Leishmanicidal activities of novel synthetic furoxan and benzofuroxan derivatives
Dutra, Luiz Ant?nio,De Almeida, Letícia,Passalacqua, Thais G.,Reis, Juliana Santana,Torres, Fabio A. E.,Martinez, Isabel,Peccinini, Rosangela Gon?alves,Chin, Chung Man,Chegaev, Konstantin,Guglielmo, Stefano,Fruttero, Roberta,Graminha, Marcia A. S.,Dos Santos, Jean Leandro
, p. 4837 - 4847 (2014)
A novel series of furoxan (1,2,5-oxadiazole 2-oxide) (compounds 3, 4a and -b, 13a and -b, and 14a to -f) and benzofuroxan (benzo[c][1,2,5]oxadiazole 1-oxide) (compounds 7 and 8a to -c) derivatives were synthesized, characterized, and evaluated for in vitro activity against promastigote and intracellular amastigote forms of Leishmania amazonensis. The furoxan derivatives exhibited the ability to generate nitric oxide at different levels (7.8% to 27.4%). The benzofuroxan derivative 8a was able to increase nitrite production in medium supernatant from murine macrophages infected with L. amazonensis at 0.75 mM after 48 h. Furoxan and benzofuroxan derivatives showed remarkable leishmanicidal activity against both promastigote and intracellular amastigote forms. Compounds 8a, 14a and -b, and 14d exerted selective leishmanicidal activities superior to those of amphotericin B and pentamidine. In vitro studies at pH 5.4 reveal that compound 8a is stable until 8 h and that compound 14a behaves as a prodrug, releasing the active aldehyde 13a. These compounds have emerged as promising novel drug candidates for the treatment of leishmaniasis. Copyright
Arenediazothioalkanoic (Arylazothioalkanoic) acids by coupling of arenediazonium compounds with 2-Mercaptoalkanoic acids
Buglass, Alan J.,Datta, Mrityunjoy
, p. 218 - 224 (2018)
The title compounds–arenediazothioethanoic acids and 2-arenediazothiopropanoic acids–have been synthesized by the coupling of arenediazonium phosphates with 2-mercaptoacetic or 2-mercaptopropanoic acid in aqueous media at pH ～ 4. Included are hitherto unreported benzenediazothioethanoic acid and 2-benzenediazothiopropanoic acid prepared in pure form, as well as a number of mostly para ring-substituted examples. Mass spectral fragmentation patterns of selected title compounds are discussed, along with a brief preliminary account of their Z/E-isomerization and thermal stabilities.
3-Thiolated 2-azetidinones: Synthesis and in vitro antibacterial and antifungal activities
Zarei, Maaroof,Mohamadzadeh, Masoud
, p. 5832 - 5840 (2011)
A series of 3-thiolated β-lactams were synthesized by [2+2] ketene-imine cycloaddition reaction from S-substituted mercaptoacetic acids and Schiff bases. Then, some of the 3-methylthio β-lactams were converted to 3-(methylsulfinyl) β-lactams and 3-(methylsulfonyl) β-lactams using m-CPBA under different reaction conditions. All the compounds were characterized by spectral data and elemental analyses and were evaluated for their in vitro antibacterial and antifungal activities against pathogenic strains including Staphylococcus aureus (Methicillin resistant strain). The preliminary screening results indicated that some of these compounds demonstrated moderate to very good antibacterial and antifungal activities.
Design and synthesis of furoxan-based nitric oxide-releasing glucocorticoid derivatives with potent anti-inflammatory activity and improved safety
Fang, Lei,Zhang, Yihua,Lehmann, Jochen,Wang, You,Ji, Hui,Ding, Dayong
, p. 1062 - 1066 (2007)
A series of furoxan-based nitric oxide-releasing glucocorticoid derivatives was synthesized. The pharmacological assays indicated that three compounds, including I4, I5, and I6, had anti-inflammatory activity. Furthermore compared with the leading compound hydrocortisone the safety of I6 was greatly improved. Due to releasing NO in vivo the side effects of glucocorticoids, including hypertension and osteoporosis, were effectively avoided.
Novel NO-releasing scopoletin derivatives induce cell death via mitochondrial apoptosis pathway and cell cycle arrest
Chen, Cheng,Chen, Li,Lei, Zhichao,Li, Na,Shi, Zhixian,Sun, Jianbo,Wang, Yujin
, (2020)
A series of phenylsulfonyfuroxan-based NO-releasing scopoletin derivatives were designed and synthesized in the study. All target compounds showed significantly improved antiproliferative activity against four cancer cell lines (MDA-MB-231, MCF-7, HepG2 and A459) and lower cytotoxicity toward normal liver LO2 cells. Derivative 47 concentration-dependently inhibited the colony formation of MDA-MB-231 cells. NO-releasing assessment indicated that the intracellular NO level was almost positively correlated with the antiproliferative ability. Compound 47, which released the highest amounts of NO, showed the best potency (IC50 = 1.23 μM) against MDA-MB-231 cells. Mechanism research revealed for the first time that 47 blocked the proliferation of MDA-MB-231 cells by activating mitochondrial apoptosis pathway and arresting cell cycle at G2/M phase. Taken together, as a novel scopoletin derivative, 47 exhibited excellent inhibitory effects against malignant cancer cells and lower toxicity on normal cells. Thus, an in-depth evaluation of 47 to explore its complete therapeutic potential for cancer treatment is warranted.
Antiproliferative chromone derivatives induce K562 cell death through endogenous and exogenous pathways
Cao, Hao,Hua, Huiming,Huang, Xiaofang,Jiao, Runwei,Li, Dahong,Li, Haonan,Li, Zhanlin,Liu, Weiwei,Xu, Fanxing,Zang, Linghe
, p. 759 - 772 (2020)
A series of furoxan derivatives of chromone were prepared. The antiproliferative activities were tested against five cancer cell lines HepG2, MCF-7, HCT-116, B16, and K562, and two normal human cell lines L-02 and PBMCs. Among them, compound 15a exhibited the most potent antiproliferative activity. It was also found 15a produced more than 8 μM of NO at the peak time of 45 min by Griess assay. Generally, antiproliferative activity is positively related to NO release to some extent. Further in-depth studies on apoptosis-related mechanisms showed that 15a caused S-phase cell cycle arrest in a concentration-dependent manner and induced apoptosis significantly through mitochondria-related pathways. Human apoptosis protein array assay also demonstrated 15a increased the expression levels of pro-apoptotic Bax, Bad, HtrA2 and Trail R2/DR5. The expression of catalase and cell cycle blocker claspin were similarly up-regulated. In balance, 15a induced K562 cells death through both endogenous and exogenous pathways.
Oxidation of Organic Sulfides by Permanganate Ion
Lee, Donald G.,Chen, Tao
, p. 5346 - 5348 (1991)
The current literature on the oxidation of sulfides by permanganate contains a suggestion that the reaction mechanism involves an electrophilic oxygen transfer in an SN2-like mechanism.Contrary to this assumption, it is argued that the experimental facts obtained from a study of the oxidation of (arylthio)acetic acids can more reasonably be accommodated in a mechanism that is initiated by the formation of a coordinate covalent bond utilizing an unshared pair of sulfur electrons and empty manganese d-orbitals.Rearrangement of this intermediate then leads to the formation of sulfoxide and manganate(V) ion.
Design, synthesis and apoptosis-related antiproliferative activities of chelidonine derivatives
Cheng, Keguang,Gao, Xiang,Hu, Xu,Hua, Huiming,Huang, Xueyan,Li, Dahong,Li, Haonan,Li, Zhanlin,Liu, Lilin,Xu, Fanxing
, (2019)
To get chelidonine derivatives with enhanced antiproliferative activity and selectivity, a series of nitric oxide donating derivatives (10a-f and 11a-j) were designed, synthesized and biologically evaluated. Compared with chelidonine, these compounds exhibited lower IC50 values against human hepatoma cells HepG2, breast cancer cells MCF-7, colon cancer cells HCT-116, as well as leukemia cells K562. Compound 11j displayed the strongest antiproliferative activity with IC50 values of 3.91, 6.90, 4.36 and 1.12 μM against the above four cells, respectively. Nevertheless, it showed an IC50 value >40 μM against human peripheral blood mononuclear cells (PBMCs), which demonstrated high selectivity between normal and cancer blood cells. In further mechanism studies, 11j showed the capability to induce K562 cells apoptosis, S phase cell cycle arrest and mitochondrial membrane potential disorder. Besides, 11j was found to be effective in promoting the expression of proapoptotic protein Bad and suppressing the expression of anti-apoptotic proteins Bcl-xL, catalase, survivin, claspin and clusterin.
