1904-58-1Relevant articles and documents
Barbiturate bearing aroylhydrazine derivatives: Synthesis, NMR investigations, single crystal X-ray studies and biological activity
Giziroglu, Emrah,Sarikurkcu, Cengiz,Aygün, Muhittin,Basbulbul, Gamze,Soyleyici, H. Can,Firinci, Erkan,Kirkan, Bulent,Alkis, Ayse,Saylica, Tayfur,Biyik, Halil
, p. 325 - 333 (2016)
A series of barbituric acid aroylhydrazine derivatives have been prepared from their corresponding 1,3-dimethyl-5-acetyl barbituric acid and aroylhydrazines. All compounds have been fully characterized by using FT-IR, multinuclear NMR (1H, 13C) and Mass (MS) spectrometry. We also describe the X-ray crystal structure of 3a, which crystallizes in the monoclinic P21/n space group. The crystal structure is stabilized with infinite linear chains of dimeric units. Furthermore, all compounds were investigated for their tyrosinase inhibition, antioxidative and antimicrobial activies. The results from biological activity assays have shown that all of compounds have excellent antioxidant, significant tyrosinase inhibition and moderate antimicrobial activity.
Synthesis and characterization of novel M(II) (M = Mn(II), Ni(II), Cu(II) or Zn(II)) complexes with tridentate N2, O-donor ligand (E)-2-amino-N'-[1-(pyridin-2-yl)ethylidene]benzohydrazide
Kane, Cheikh Hamidou,Tinguiano, Daniel,Tamboura, Farba Bouyagui,Thiam, Ibrahima Elhadj,Barry, Aliou Hamady,Gaye, Mohamed,Retailleau, Pascal
, p. 101 - 110 (2016)
The coordination chemistry towards the M(II) metal centre (M = Mn, Ni, Cu or Zn) of the hydrazone ligand (E)-2-amino-N'-[1-(pyridin-2-yl)ethylidene]benzohydrazide (H3L) has been explored and complexes having formulae [Mn(H2L)2] (1), {[Ni(H2L)2].DMF.0.4H2O} (2), {[Cu2(H2L)2(μ-Cl)2].DMF} (3) and [Zn(H2L)2] (4) have been isolated and characterized by IR, UV-Visible spectroscopy, elemental analysis and Xray crystal diffraction. Structural studies reveal that the mononuclear complexes (1), (2) and (4) adopt highly distorted octahedral geometries while the dinuclear complex (3) adopts a square pyramidal geometry around each copper(II) ion.
Room-temperature switching of magnetic hysteresis by reversible single-crystal-to-single-crystal solvent exchange in imidazole-inspired Fe(II) complexes
Huang, Wei,Shen, Fuxing,Zhang, Ming,Wu, Dayu,Pan, Feifei,Sato, Osamu
, p. 14911 - 14918 (2016)
The recent upsurge in molecular magnetism reflects its application in the areas of sensors and molecular switches. Thermal hysteresis is crucial to the molecular bistability and information storage, a wide hysteresis near room temperature is expected to be of practical sense for the molecular compound. In this work, spin crossover iron(ii) complexes [Fe(Liq)2](BF4)2·(CH3CH2)2O (1-Et2O) and [Fe(Liq)2](BF4)2·3H2O (1-3H2O) were prepared and structurally and magnetically analysed. The single-crystal-to-single-crystal (SCSC) solvation transformation and the influence on the crystal structures and magnetic hysteresis were investigated in an etherification-hydration cycle. At room temperature, X-ray diffraction experiments indicated a transformation from one crystal (1-Et2O, P21212) to another crystal (1-3H2O, P212121) upon humidity exposure and reversible recovery of its crystallinity upon exposure to ether vapor. The etherified phase 1-Et2O exhibits room temperature spin crossover (T1/2 = 305 K) but negligible thermal hysteresis, however the hydrated phase 1-3H2O exhibits the apparent hysteresis loop (T1/2↑ = 346 K, T1/2↓ = 326 K) which expands to room temperature. This effect is associated with the change of intermolecular cooperativity in the etherification-hydration recyclability.
Synthesis, spectral characterization and thermal studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes with 2-amino benzoic acid- and 2-hydroxy benzoic acid thiophen-2-ylmethylene hydrazide
Singh, Vinod P.,Singh, Pooja
, p. 363 - 370 (2013)
A series of metal complexes of Co(II), Ni(II), Cu(II) and Zn(II) with 2-amino benzoic acid thiophen-2-ylmethylene hydrazide (Habth) and 2-hydroxy benzoic acid thiophen-2-ylmethylene hydrazide (Hhbth) have been synthesized. The complexes were characterized by elemental analyses, molar conductance, magnetic susceptibility measurements, electronic, IR, NMR, ESR spectra and thermal studies (TGA and DTA). Molecular structure of the Habth ligand was determined by single crystal X-ray diffraction technique. Habth acts as a monobasic bidentate ligand in all its complexes bonding through a deprotonated CO- and CN groups whereas, Hhbth acts as a monobasic bidentate in its Co(II) and Ni(II) complexes, bonding through a deprotonated CO- and CN groups and as monobasic tridentate in Cu(II) and Zn(II) complexes bonding through CO, CN and deprotonated (CO)- groups with the metal ion. Electronic spectra suggest a square planar geometry for Co(II), Ni(II) and Cu(II) complexes of Habth and Co(II) and Ni(II) complexes of Hhbth. However, the Cu(II) and Zn(II) complexes of Hhbth have octahedral geometry. The ESR spectra of Cu(II) complex of Hhbth in the solid state and in DMSO frozen solution show axial signals and suggest the presence of unpaired electron in dx2-y2 orbital of Cu(II). The Cu(II) complex of Habth in solid state shows isotropic signal, whereas, axial signal in DMSO frozen solution in the range of tetragonally distorted octahedral geometry due to interactions of DMSO molecules at axial positions. Thermal studies of some of the metal complexes show a multi-step decomposition pattern of bonded ligands in the complex.
Pyridazino[1,6-b]quinazolinones as new anticancer scaffold: Synthesis, DNA intercalation, topoisomerase I inhibition and antitumor evaluation in vitro and in vivo
Huang, Wan-Yun,Zhang, Xiao-Rong,Lyu, Liang,Wang, Shu-Qin,Zhang, Xiao-Ting
, (2020)
A new anticancer N-containing heterocyclic scaffold was designed and 30 pyridazino[1,6-b]quinazolinone derivatives were synthesized and characterized. Antiproliferation evaluation in vitro against four human cancer cell lines including SK-OV-3(ovarian cell), CNE-2(nasopharyngeal cell), MGC-803(gastric cell) and NCI-H460(lung cell) indicated that most of them exhibited potent anticancer activity and the IC50 value of the most potent compound lowered to sub-μM. DNA interaction assay indicated that compounds 4e, 4g, 6o, 6p, 8o can intercalate into DNA. Compounds 6 and 8 also demonstrated potent topoisomerase I (topo I) activity. Annexin V- FITC/propidium iodide dual staining assay and cell cycle analysis indicated that 2-(4-bromophenyl)-4-((3-(diethylamino)propyl)amino) ?10H-pyridazino [1,6-b]quinazolin- 10-one (8p) could induce arrest cell cycle at G2 phase and apoptosis in MGC-803 cells in a dose-dependent manner. The in vivo antitumor efficiency of compound 8p was also evaluated on MGC-803 xenograft nude mice, and the relative tumor growth inhibition was up to 55.9% at a dose of 20 mg/kg per two days. The results suggested that pyridazino[1,6-b]-quinazolinones might serve as a promising novel scaffold for the development of new antitumor agents.
Mononuclear late first row transition metal complexes of ONO donor hydrazone ligand: Synthesis, characterization, crystallographic insight, in vivo and in vitro anti-inflammatory activity
Kendur, Umashri,Chimmalagi, Geeta H.,Patil, Sunil M.,Gudasi, Kalagouda B.,Frampton, Christopher S.,Mangannavar, Chandrashekhar V.,Muchchandi, Iranna S.
, p. 299 - 310 (2018)
Air and moisture stable coordination compounds of late first row transition metal ions, viz., Co(II), Ni(II), Cu(II) and Zn(II) with a newly designed ligand, (E)-2-amino-N'-(1-(2-hydroxy-6-methyl-4-oxo-4H-pyran-3-yl)ethylidene)benzohydrazide (H2L) were prepared and extensively characterized using various spectro-analytical techniques. The ligand acts both in mono as well as doubly deprotonated manner. The ligand to metal stoichiometry was found to be 1:2 in case of complexes using chloride salts, whereas 1:1 in case of copper (II) complex using its acetate salt. The molecular structures of H2L, nickel and copper complexes were unambiguously determined by single-crystal X-ray diffraction studies reveal that H2L exists in a zwitterionic form while copper complex has copper centre in a distorted square planar environment. On the other hand, cobalt, nickel and zinc complexes display distorted octahedral coordination around the metal ion. In case of [Ni(HL)2].H2O, intramolecular C–H?π stacking interaction were observed between the centroid of five membered chelate ring and phenyl proton C5–H5 and intermolecular C–H?π stacking interaction between the centroid of phenyl ring, dehydroacetic acid (DHA) ring and phenyl protons. The [Cu(L)DMF] complex is stabilized by intramolecular hydrogen bonding N1H?N2 and by intermolecular hydrogen bonding N1H?O4. Intermolecular interactions were investigated by Hirshfeld surfaces. Further, H2L and its metal complexes were screened for their in vivo and in vitro anti-inflammatory activities. The activity of the ligand has enhanced on coordination with transition metals. The tested compounds have shown excellent activity, which is almost equipotent to the standard used in the study.
Discovery of an Orally Efficacious MYC Inhibitor for Liver Cancer Using a GNMT-Based High-Throughput Screening System and Structure-Activity Relationship Analysis
Kant, Rajni,Yang, Ming-Hui,Tseng, Chih-Hua,Yen, Chia-Hung,Li, Wei-You,Tyan, Yu-Chang,Chen, Marcelo,Tzeng, Cherng-Chyi,Chen, Wei-Cheng,You, Kaiting,Wang, Wen-Chieh,Chen, Yeh-Long,Chen, Yi-Ming Arthur
, p. 8992 - 9009 (2021/07/19)
Glycine-N-methyl transferase (GNMT) downregulation results in spontaneous hepatocellular carcinoma (HCC). Overexpression of GNMT inhibits the proliferation of liver cancer cell lines and prevents carcinogen-induced HCC, suggesting that GNMT induction is a potential approach for anti-HCC therapy. Herein, we used Huh7 GNMT promoter-driven screening to identify a GNMT inducer. Compound K78 was identified and validated for its induction of GNMT and inhibition of Huh7 cell growth. Subsequently, we employed structure-activity relationship analysis and found a potent GNMT inducer, K117. K117 inhibited Huh7 cell growth in vitro and xenograft in vivo. Oral administration of a dosage of K117 at 10 mpk (milligrams per kilogram) can inhibit Huh7 xenograft in a manner equivalent to the effect of sorafenib at a dosage of 25 mpk. A mechanistic study revealed that K117 is an MYC inhibitor. Ectopic expression of MYC using CMV promoter blocked K117-mediated MYC inhibition and GNMT induction. Overall, K117 is a potential lead compound for HCC- and MYC-dependent cancers.
Multi-target anti-tumor small molecules and their derivatives, preparation methods, pharmaceutical compositions and applications
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Paragraph 0039-0040; 0044-0046, (2022/01/05)
The present invention discloses a class of multi-target anti-tumor small molecules and derivatives thereof, preparation methods, pharmaceutical compositions and applications. The chemical structure of such small molecules as shown in formula I, the derivative of which relates to a pharmaceutically acceptable salt of the small molecule. This class of small molecules and their derivatives has a highly efficient tumor suppressor effect in vivo and abroad, low toxicity to cells and organisms, no genotoxicity; anti-tumor activity is achieved through multi-target action, with pan-HDAC inhibitory activity, and can also effectively activate the p53 pathway, inhibit topoisomerase activity, can be used to prepare anti-tumor drugs; the preparation method is simple and easy to operate.
