共查询到20条相似文献,搜索用时 31 毫秒
1.
Trieu-Tien Thai Bruno Therrien Georg Süss-Fink 《Inorganic chemistry communications》2009,12(8):806-807
The neutral chloro complexes [(η5-C5Me5)M(η2-NC9H6O)Cl] as well as the cationic aqua complexes [(η5-C5Me5)M(η2-NC9H6O)(H2O)]+ (M = Rh, Ir) have been synthesized from the reaction of the dinuclear precursors [(η5-C5Me5)MCl2]2 and 8-hydroxyquinoline. The single crystal X-ray structure analysis of [(η5-C5Me5)Ir(η2-NC9H6O)Cl] reveals for these complexes a piano-stool arrangement with the aromatic ligand, the chelating oxinato ligand and the terminal chloro or aqua ligand surrounding the metal center in a pseudo-tetrahedral fashion. 相似文献
2.
Alice De Palo Dijana Draca Maria Grazia Murrali Stefano Zacchini Guido Pampaloni Sanja Mijatovic Danijela Maksimovic-Ivanic Fabio Marchetti 《International journal of molecular sciences》2021,22(14)
Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*) have been intensively investigated as anticancer drug candidates and hold much promise in this setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the antiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η5-C5Me4R)Cl(μ-Cl)]2 (R = Me, 1a; R = H, 1b; R = Pr, 1c; R = 4-C6H4F, 1d; R = 4-C6H4OH, 1e), their 2-phenylpyridyl mononuclear derivatives [Ir(η5-C5Me4R)(kN,kCPhPy)Cl] (2a–d), and the dimethylsulfoxide complex [Ir{η5-C5Me4(4-C6H4OH)}Cl2(κS-Me2S=O)] (3) were synthesized, structurally characterized, and assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5). Complexes 2b (R = H) and 2d (4-C6H4F) emerged as the most active ones and were selected for further investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumoricidal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species. 相似文献
3.
Padavattan Govindaswamy Georg Süss-Fink Bruno Therrien 《Inorganic chemistry communications》2007,10(12):1489-1492
Two cationic pentamethylcyclopentadienyl metal-based hexanuclear complexes with trigonal prismatic architecture have been synthesised through a two-step strategy. The dinuclear complexes [M(η5- C5Me5)(μ-Cl)Cl]2 (M = rhodium and iridium) react with 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine (tpt) in dichloromethane to give the trinuclear complexes [Rh3(η5-C5Me5)3(μ3-tpt)Cl6] (1) and [Ir3(η5-C5Me5)3(μ3-tpt)Cl6] (2), respectively. Addition of silver triflate to 1 and 2 in dichloromethane connects two identical triangular panels to form the hexanuclear metallo-prismatic cations [Rh6(η5-C5Me5)6(μ3-tpt)2(μ-Cl)6]6+ (3) and [Ir6(η5-C5Me5)6(μ3-tpt)2(μ-Cl)6]6+ (4), respectively. Cations 3 and 4 have been isolated as their triflate salts and characterised by 1H NMR, IR and UV/visible spectroscopy. 相似文献
4.
Agnieszka Jaboska-Wawrzycka Patrycja Rogala Grzegorz Czerwonka Katarzyna Gaczyska Marcin Drabik Magdalena Daczuk 《International journal of molecular sciences》2021,22(18)
Antimicrobial resistance is a growing public health concern that requires urgent action. Biofilm-associated resistance to antimicrobials begins at the attachment phase and increases as the biofilms maturate. Hence, interrupting the initial binding process of bacteria to surfaces is essential to effectively prevent biofilm-associated problems. Herein, we have evaluated the antibacterial and anti-biofilm activities of three ruthenium complexes in different oxidation states with 2-pyridin-2-yl-1H-benzimidazole (L1 = 2,2′-PyBIm): [(η6-p-cymene)RuIIClL1]PF6 (Ru(II) complex), mer-[RuIIICl3(CH3CN)L1]·L1·3H2O (Ru(III) complex), (H2L1)2[RuIIICl4(CH3CN)2]2[RuIVCl4(CH3CN)2]·2Cl·6H2O (Ru(III/IV) complex). The biological activity of the compounds was screened against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa strains. The results indicated that the anti-biofilm activity of the Ru complexes at concentration of 1 mM was better than that of the ligand alone against the P. aeruginosa PAO1. It means that ligand, in combination with ruthenium ion, shows a synergistic effect. The effect of the Ru complexes on cell surface properties was determined by the contact angle and zeta potential values. The electric and physical properties of the microbial surface are useful tools for the examined aggregation phenomenon and disruption of the adhesion. Considering that intermolecular interactions are important and largely define the functions of compounds, we examined interactions in the crystals of the Ru complexes using the Hirshfeld surface analysis. 相似文献
5.
Stephan Back Wolfgang Frosch Ignacio del Río Gerard van Koten Heinrich Lang 《Inorganic chemistry communications》1999,2(12):162
Heterotrinuclear Ti–Cu–Ru (5) and heterotetranuclear Ti–Cu–Pt–Fe (7) containing complexes are accessible by using {[Ti](CCtBu)2}CuMe (1) ([Ti]=(η5-C5H4SiMe3)2Ti) as key molecule; in 5 and 7, the corresponding early and late transition metal atoms are linked by π-conjugated organic moieties. 相似文献
6.
《Inorganic chemistry communications》2002,5(10):862-864
Alkenyl-phosphonio complexes of ruthenium(II), rhodium(III) and iridium(III) were prepared by reactions of [(p-cymene)RuCl2(PPh3)] or [Cp*MCl2(PPh3)] (M=Rh, Ir; Cp*=C5Me5) with 1-ethynylbenzene and triphenylphosphine in the presence of KPF6. 相似文献
7.
Man-Yi Ye Gui-Yang Yao Jing-Chen Wei Ying-Ming Pan Zhi-Xin Liao Heng-Shan Wang 《International journal of molecular sciences》2013,14(5):9424-9439
Several rhein-phosphonate derivatives (5a–c) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially compounds 5b exhibited the strongest cytotoxicity against HepG-2 and Spca-2 cells (IC50 was 8.82 and 9.01 μM), respectively. All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. Further experiments proved that 5b could disturb the cell cycle in HepG-2 cells and induce apoptosis. In addition, the binding properties of a model conjugate 5b to DNA were investigated by methods (UV-Vis, fluorescence, CD spectroscopy). Results indicated that 5b showed moderate ability to interact ct-DNA. 相似文献
8.
Oscar A. Lenis-Rojas Catarina Roma-Rodrigues Alexandra R. Fernandes Andreia Carvalho Sandra Cordeiro Jorge Guerra-Varela Laura Snchez Digna Vzquez-García Margarita Lpez-Torres Alberto Fernndez Jesús J. Fernndez 《International journal of molecular sciences》2021,22(16)
The clinical success of cisplatin, carboplatin, and oxaliplatin has sparked the interest of medicinal inorganic chemistry to synthesize and study compounds with non-platinum metal centers. Despite Ru(II)–polypyridyl complexes being widely studied and well established for their antitumor properties, there are not enough in vivo studies to establish the potentiality of this type of compound. Therefore, we report to the best of our knowledge the first in vivo study of Ru(II)–polypyridyl complexes against breast cancer with promising results. In order to conduct our study, we used MCF7 zebrafish xenografts and ruthenium complexes [Ru(bipy)2(C12H8N6-N,N)][CF3SO3]2 Ru1 and [{Ru(bipy)2}2(μ-C12H8N6-N,N)][CF3SO3]4 Ru2, which were recently developed by our group. Ru1 and Ru2 reduced the tumor size by an average of 30% without causing significant signs of lethality when administered at low doses of 1.25 mg·L−1. Moreover, the in vitro selectivity results were confirmed in vivo against MCF7 breast cancer cells. Surprisingly, this work suggests that both the mono- and the dinuclear Ru(II)–polypyridyl compounds have in vivo potential against breast cancer, since there were no significant differences between both treatments, highlighting Ru1 and Ru2 as promising chemotherapy agents in breast cancer therapy. 相似文献
9.
Li Zhang Lei Wang Xiao-Yan Ma Rui-Xiang Li Xian-Jun Li 《Catalysis communications》2007,8(12):2238-2242
The influences of pH on the catalytic properties of Ru-η6-C6H6-diphosphine complex [RuCl(η6-C6H6)(BISBI)]Cl (1) (BISBI = 2,2′-bis(diphenylphosphinomethyl)-1,1′-biphenyl), [RuCl(η6-C6H6)(BDPX)]Cl (2) (BDPX = 1,2-bis(diphenylphosphinomethyl)benzene), Ru2Cl4(η6-C6H6)2(μ2-BDNA) (3) (BDNA = 1,8-bis(diphenylphosphinomethyl)naphthalene), [RuCl(η6-C6H6)(BISBI)]BF4 (4), [RuCl(η6-C6H6)(BDPX)]BF4 (5), and [(η6-C6H6)2Ru2Cl2(μ2-Cl)(μ2-BDNA)]BF4 (6) for the hydrogenation of benzene were investigated in aqueous-organic biphasic system. The hydrogenation of benzene catalyzed by all complexes yielded only cyclohexane. The catalytic results revealed that the stabilities of these complexes were not only closely relative with their compositions or molecular structures but also the pH value of aqueous solution. Complexes 1 and 2 were homogeneous catalysts at pH <5, but complexes 3, 4, 5 and 6 were partly decomposed in the same reaction conditions and played simultaneously the roles of homogeneous and heterogeneous catalysts. When the pH was up to 12, all of six complexes were gradually decomposed to Ru(0) particles. The addition of extra phosphine ligand was favorable to prevent these complexes from decomposing in the catalytic process. The experiment of mercury poisoning and the curve of conversion vs time strongly supported above conclusions. 相似文献
10.
Mala A. Sainna Sam P. de Visser 《International journal of molecular sciences》2015,16(10):23369-23381
Industrial Fischer-Tropsch processes involve the synthesis of hydrocarbons usually on metal surface catalysts. On the other hand, very few homogeneous catalysts are known to perform a Fischer-Tropsch style of reaction. In recent work, we established the catalytic properties of a diruthenium-platinum carbene complex, [(CpRu)2(μ2-H)(μ2-NHCH3)(μ3-C)PtCH3(P(CH3)3)2](CO)n+ with n = 0, 2 and Cp = η5-C5(CH3)5, and showed it to react efficiently by initial hydrogen atom transfer followed by methyl transfer to form an alkyl chain on the Ru-center. In particular, the catalytic efficiency was shown to increase after the addition of two CO molecules. As such, this system could be viewed as a potential homogeneous Fischer-Tropsch catalyst. Herein, we have engineered the catalytic center of the catalyst and investigated the reactivity of trimetal carbene complexes of the same type using iron, ruthenium and osmium at the central metal scaffold. The work shows that the reactivity should increase from diosmium to diruthenium to diiron; however, a non-linear trend is observed due to multiple factors contributing to the individual barrier heights. We identified all individual components of these reaction steps in detail and established the difference in reactivity of the various complexes. 相似文献
11.
Jn Van
o Zdenk Trvní
ek Jan Hoek Tom Malina Zdenk Dvok 《International journal of molecular sciences》2021,22(14)
A series of new heteroleptic copper(II) complexes of the composition [Cu(L)(bpy)]NO3·2MeOH (1), [Cu(L)(dimebpy)]NO3·2H2O (2), [Cu(L)(phen)]NO3·2MeOH (3), [Cu(L)(bphen)]NO3·MeOH (4), [Cu(L)(dppz)]NO3·MeOH (5) was prepared, where HL = 3-(3,4-dihydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4H,8H-benzo[1,2-b:3,4-b′]dipyran-4-one, (pomiferin) and bpy = 2,2′-bipyridine, dimebpy = 4,4′-dimethyl-2,2′-bipyridine, phen = 1,10-phenanthroline, bphen = 4,7-diphenyl-1,10-phenanthroline, and dppz = dipyrido[3,2-a:2′,3′-c]phenazine. The complexes were characterized using elemental analysis, infrared and UV/Vis spectroscopies, mass spectrometry, thermal analysis and conductivity measurements. The in vitro cytotoxicity, screened against eight human cancer cell lines (breast adenocarcinoma (MCF-7), osteosarcoma (HOS), lung adenocarcinoma (A549), prostate adenocarcinoma (PC-3), ovarian carcinoma (A2780), cisplatin-resistant ovarian carcinoma (A2780R), colorectal adenocarcinoma (Caco-2) and monocytic leukemia (THP-1), revealed the complexes as effective antiproliferative agents, with the IC50 values of 2.2–13.0 μM for the best performing complexes 3 and 5. All the complexes 1–5 showed the best activity against the A2780R cells (IC50 = 2.2–6.6 μM), and moreover, the complexes demonstrated relatively low toxicity on healthy human hepatocytes, with IC50 > 100 μM. The complexes were evaluated by the Annexin V/propidium iodide apoptosis assay, induction of cell cycle modifications in A2780 cells, production of reactive oxygen species (ROS), perturbation of mitochondrial membrane potential, inhibition of apoptosis and inflammation-related signaling pathways (NF-κB/AP-1 activity, NF-κB translocation, TNF-α secretion), and tested for nuclease mimicking activity. The obtained results revealed the corresponding complexes to be effective antiproliferative and anti-inflammatory agents. 相似文献
12.
《Inorganic chemistry communications》2008,11(10):1202-1204
The [7-Me3N-nido-7-CB10H12] (1), after being treated with two molar equiv. of Proton Sponge, reacts with [(η4-C10H12)2Rh2(μ-Cl)2] (2) in benzene–ethanol solution affording two isomeric monocarbon (η-dicyclopentenyl)-closo-rhodacarborane complexes, differing in hapticity of the carbocyclic ligand, viz. [2,2-{(2′,3′-η2):(5′-η1)-C10H13}-1-(Me3N)-2,1-closo-RhCB10H10] (3) and [2-{(1′-3′-η3)-C10H13}-1-(Me3N)-2,1-closo-RhCB10H10] (4). Isomeric compounds 3 and 4 were characterized by analytical, multinuclear NMR spectroscopic data as well as by single-crystal X-ray diffraction study, which revealed the existence of an agostic C–H⋯Rh interaction in both the species. 相似文献
13.
Floyd A. Beckford Gabriel Leblanc Jeffrey Thessing Michael Shaloski Brian J. Frost Liya Li Navindra P. Seeram 《Inorganic chemistry communications》2009,12(11):1094-1098
A series of half-sandwich arene ruthenium complexes containing bidentate thiosemicarbazone ligands have been synthesized and their biological activity investigated. The compounds have the general formula [(6-p-cymene)Ru(R-ATSC)Cl]X (ATSC = 9-anthraldehyde thiosemicarbazone and R = H, CH3 and C6H5). The crystal structure of [(6-p-cymene) Ru(MeATSC)Cl]Cl have been determined and represents the first structurally characterized arene–ruthenium half-sandwich complex with a thiosemicarbazone ligand. The complexes show good cytotoxic profiles against MCF-7 and MDA-MB-231 (breast adenocarcinoma) as well as HCT 116 and HT-29 (colorectal carcinoma) cell lines. 相似文献
14.
Ekaterina A. Litus Alexey S. Kazakov Evgenia I. Deryusheva Ekaterina L. Nemashkalova Marina P. Shevelyova Aliya A. Nazipova Maria E. Permyakova Elena V. Raznikova Vladimir N. Uversky Sergei E. Permyakov 《International journal of molecular sciences》2021,22(11)
Prevention of amyloid β peptide (Aβ) deposition via facilitation of Aβ binding to its natural depot, human serum albumin (HSA), is a promising approach to preclude Alzheimer’s disease (AD) onset and progression. Previously, we demonstrated the ability of natural HSA ligands, fatty acids, to improve the affinity of this protein to monomeric Aβ by a factor of 3 (BBRC, 510(2), 248–253). Using plasmon resonance spectroscopy, we show here that another HSA ligand related to AD pathogenesis, serotonin (SRO), increases the affinity of the Aβ monomer to HSA by a factor of 7/17 for Aβ40/Aβ42, respectively. Meanwhile, the structurally homologous SRO precursor, tryptophan (TRP), does not affect HSA’s affinity to monomeric Aβ, despite slowdown of the association and dissociation processes. Crosslinking with glutaraldehyde and dynamic light scattering experiments reveal that, compared with the TRP-induced effects, SRO binding causes more marked changes in the quaternary structure of HSA. Furthermore, molecular docking reveals distinct structural differences between SRO/TRP complexes with HSA. The disintegration of the serotonergic system during AD pathogenesis may contribute to Aβ release from HSA in the central nervous system due to impairment of the SRO-mediated Aβ trapping by HSA. 相似文献
15.
Mathiyazhagan Ulaganatha Raja Elangovan Sindhuja Rengan Ramesh 《Inorganic chemistry communications》2010,13(11):1321-1324
A series of cationic half-sandwich arene ruthenium(II) complexes of general formula [Ru(η6-p-cymene)Cl(L)]Cl have been synthesized from the reaction of [Ru(η6-p-cymene)Cl2]2 with thiosemicarbazone derivatives (L). Characterization of the complexes were accomplished by analytical and spectral (FT-IR, UV–Vis, 1H NMR) methods. Single crystal structure determination reveals the presence of a pseudooctahedral three-legged piano stool conformation. All the complexes exhibit a quasi-reversible one electron reduction in the range from ?0.75 to ?0.85 V. Further, the catalytic activity of the titled complex has been investigated in the transfer hydrogenation of ketones in the presence of isopropanol/NaOH. 相似文献
16.
Reaction of the complexes [RuCl2(PPh3)L] (L = η6-p-cymene or η6-hexamethylbenzene) with N-cyanoacetylurethane [NCCH2C(O)NHCO2Et] and tertiary amine base in refluxing methanol gives the first examples of mononuclear complexes containing the four-membered ruthenalactam ring, Ru–C–C(O)–N. The complexes were characterised by 1H and 31P{1H} NMR spectroscopy and ESI mass spectrometry. A single-crystal X-ray diffraction study on the p-cymene complex showed the four-membered ruthenalactam ring to be planar. 相似文献
17.
Patricia B. da Silva Paula C. de Souza Giovana Maria Fioramonti Calixto Erica de O. Lopes Regina C. G. Frem Adelino V. G. Netto Antonio E. Mauro Fernando R. Pavan Marlus Chorilli 《International journal of molecular sciences》2016,17(5)
Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis (Mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. The aim of this study was to evaluate a nanostructured lipid system (NLS) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and Eumulgin® HRE 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer pH = 7.4) as a tactic to enhance the in vitro anti-Mtb activity of the copper(II) complexes [CuCl2(INH)2]·H2O (1), [Cu(NCS)2(INH)2]·5H2O (2) and [Cu(NCO)2(INH)2]·4H2O (3). The Cu(II) complex-loaded NLS displayed sizes ranging from 169.5 ± 0.7095 to 211.1 ± 0.8963 nm, polydispersity index (PDI) varying from 0.135 ± 0.0130 to 0.236 ± 0.00100, and zeta potential ranging from −0.00690 ± 0.0896 to −8.43 ± 1.63 mV. Rheological analysis showed that the formulations behave as non-Newtonian fluids of the pseudoplastic and viscoelastic type. Antimycobacterial activities of the free complexes and NLS-loaded complexes against Mtb H37Rv ATCC 27294 were evaluated by the REMA methodology, and the selectivity index (SI) was calculated using the cytotoxicity index (IC50) against Vero (ATCC® CCL-81), J774A.1 (ATCC® TIB-67), and MRC-5 (ATCC® CCL-171) cell lines. The data suggest that the incorporation of the complexes into NLS improved the inhibitory action against Mtb by 52-, 27-, and 4.7-fold and the SI values by 173-, 43-, and 7-fold for the compounds 1, 2 and 3, respectively. The incorporation of the complexes 1, 2 and 3 into the NLS also resulted in a significant decrease of toxicity towards an alternative model (Artemia salina L.). These findings suggest that the NLS may be considered as a platform for incorporation of metallic complexes aimed at the treatment of TB. 相似文献
18.
《Inorganic chemistry communications》1999,2(11):524-526
Homoleptic Ru(II)–diphosphine and Ru(II)–diarsine complexes [Ru(L-L)3](OTf)2 (L-L=Me2P(CH2)nPMe2; n=1, dmpm; n=2, dmpe) and 1,2-C6H4(AsMe2)2 (diars) have been isolated, in which the Ru(II) state is stabilised to an unprecedented degree, and the crystal structure of [Ru(diars)3]Cl2 has been determined. 相似文献
19.
Taryn M. Golding Dr. Reinner O. Omondi Dr. Supratim Biswas Dr. Suparna Chakraborty Prof. Sharon Prince Prof. Gregory S. Smith 《Chembiochem : a European journal of chemical biology》2023,24(13):e202300271
The increased success of small metal-containing molecules as pharmaceutical agents has prompted investigations into the pharmacological activity of a different class of metal-based compounds; supramolecular coordination complexes (SCCs). Such complexes have been extensively investigated for their anticancer activity, with many displaying activities comparable or superior to available clinical chemotherapeutic drugs. Here, we evaluated a series of quinoline-containing binuclear complexes and metallarectangles for their in vitro anticancer activity in the hormone receptor positive MCF-7 and triple negative MDA-MB-231 breast cancer cell lines. The preliminary cytotoxic screen, in the MCF-7 cell line, revealed that the ligand (7-chloro-4-(pyridin-4-yl)quinoline, L ) and metallarectangle [{Ir(μ-Cl)(Cp*)}4(μ- L )2](OTf)4 display superior activity to cisplatin, while [{Ru(p-cymene)}4(μ-η2-η2-C2O4)2(μ- L )2](OTf)4 was more potent than cisplatin in the triple-negative MDA-MD-231 cell line. Upon evaluation in a multidose screen, ligand L and metallarectangle [{Ir(μ-Cl)(Cp*)}4(μ- L )2](OTf)4 displayed antiproliferative activity almost two-fold greater than cisplatin in the MCF-7 cell line, while [{Ru(p-cymene)}4(μ-η2-η2-C2O4)2(μ- L )2](OTf)4 was over two-times more active than cisplatin in the MDA-MB-231 cell line. Additionally, using the non-tumorigenic MCF-12 A breast epithelial cell line, the compounds demonstrate increased selectivity toward breast cancer cells over non-tumorigenic cells. Furthermore, investigations into the interactions of ligand L and selected complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) indicate favourable binding. 相似文献
20.
Sang Chul Shin Ashraf K. El-Damasy Ju Hyeon Lee Seon Hee Seo Ji Hyun Kim Young Ho Seo Yuri Lee Ji Hoon Yu Eun Kyoung Bang Eunice EunKyeong Kim Gyochang Keum 《International journal of molecular sciences》2020,21(24)
Inhibition of the molecular chaperone heat shock protein 90 (Hsp90) represents a promising approach for cancer treatment. BIIB021 is a highly potent Hsp90 inhibitor with remarkable anticancer activity; however, its clinical application is limited by lack of potency and response. In this study, we aimed to investigate the impact of replacing the hydrophobic moiety of BIIB021, 4-methoxy-3,5-dimethylpyridine, with various five-membered ring structures on the binding to Hsp90. A focused array of N7/N9-substituted purines, featuring aromatic and non-aromatic rings, was designed, considering the size of hydrophobic pocket B in Hsp90 to obtain insights into their binding modes within the ATP binding site of Hsp90 in terms of π–π stacking interactions in pocket B as well as outer α-helix 4 configurations. The target molecules were synthesized and evaluated for their Hsp90α inhibitory activity in cell-free assays. Among the tested compounds, the isoxazole derivatives 6b and 6c, and the sole six-membered derivative 14 showed favorable Hsp90α inhibitory activity, with IC50 values of 1.76 µM, 0.203 µM, and 1.00 µM, respectively. Furthermore, compound 14 elicited promising anticancer activity against MCF-7, SK-BR-3, and HCT116 cell lines. The X-ray structures of compounds 4b, 6b, 6c, 8, and 14 bound to the N-terminal domain of Hsp90 were determined in order to understand the obtained results and to acquire additional structural insights, which might enable further optimization of BIIB021. 相似文献