共查询到20条相似文献,搜索用时 15 毫秒
1.
Sridevi V. Shinde Sarika Sinha Prof. Dr. Kumaravel Somasundaram Prof. Dr. Ashoka G. Samuelson 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(39):12278-12291
Neutral half‐sandwich organometallic ruthenium(II) complexes of the type [(η6‐cymene)RuCl2(L)] ( H1 – H10 ), where L represents a heterocyclic ligand, have been synthesized and characterized spectroscopically. The structures of five complexes were also established by single‐crystal X‐ray diffraction confirming a piano‐stool geometry with η6 coordination of the arene ligand. Hydrogen bonding between the N? H group of the heterocycle and a chlorine atom attached to Ru stabilizes the metal–ligand interaction. Complexes coordinated to a mercaptobenzothiazole framework ( H1 ) or mercaptobenzoxazole ( H6 ) showed high cytotoxicity against several cancer cells but not against normal cells. In vitro studies have shown that the inhibition of cancer cell growth involves primarily G1‐phase arrest as well as the generation of reactive oxygen species (ROS). The complexes are found to bind DNA in a non‐intercalative fashion and cause unwinding of plasmid DNA in a cell‐free medium. Surprisingly, the cytotoxic complexes H1 and H6 differ in their interaction with DNA, as observed by biophysical studies, they either cause a biphasic melting of the DNA or the inhibition of topoisomerase IIα activity, respectively. Substitution of the aromatic ring of the heterocycle or adding a second hydrogen‐bond donor on the heterocycle reduces the cytotoxicity. 相似文献
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Katherine M. Byrd Chitra Subramanian Jacqueline Sanchez Hashim F. Motiwala Weiya Liu Prof. Mark S. Cohen Prof. Jeffrey Holzbeierlein Prof. Brian S. J. Blagg 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(20):6921-6931
Development of heat shock protein 90 (Hsp90) C‐terminal inhibitors has emerged as an exciting strategy for the treatment of cancer. Previous efforts have focused on modifications to the natural products novobiocin and coumermycin. Moreover, variations in both the sugar and amide moieties have been extensively studied, whereas replacements for the coumarin core have received less attention. Herein, 24 cores were synthesized with varying distances and angles between the sugar and amide moieties. Compounds that exhibited good anti‐proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed the sugar and amide moieties between 7.7 and 12.1 Å apart along with angles of 180°. 相似文献
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Takuya Chiba Hidetaka Hosono Koji Nakagawa Masahiro Asaka Hiroshi Takeda Akira Matsuda Satoshi Ichikawa 《Angewandte Chemie (International ed. in English)》2014,53(19):4836-4839
The development process for syringolin A analogues having improved proteasome inhibitory and antitumor activity is described. The strategy was to first establish a convergent synthesis of syringolin A using a rare intramolecular Ugi three‐component reaction in the last stage of the synthesis, so as to gain access toa set of structure‐based analogues. The inhibitory activity of chymotrypsin‐like activity of 20S proteasome was largely improved by targeting the S3 subsite of the β5 subunit. Cytotoxic activity was also improved by installing the membrane‐permeable substituent. These biological properties are comparable to those of bortezomib, a clinically used first‐line proteasome inhibitor. 相似文献
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Dr. Yao Zhao Dr. Julie A. Woods Dr. Nicola J. Farrer Kim S. Robinson Jitka Pracharova Dr. Jana Kasparkova Olga Novakova Huilin Li Dr. Luca Salassa Dr. Ana M. Pizarro Dr. Guy J. Clarkson Dr. Lijiang Song Prof. Dr. Viktor Brabec Prof. Dr. Peter J. Sadler 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(29):9578-9591
Platinum diam(m)ine complexes, such as cisplatin, are successful anticancer drugs, but suffer from problems of resistance and side‐effects. Photoactivatable PtIV prodrugs offer the potential of targeted drug release and new mechanisms of action. We report the synthesis, X‐ray crystallographic and spectroscopic properties of photoactivatable diazido complexes trans,trans,trans‐[Pt(N3)2(OH)2(MA)(Py)] ( 1 ; MA=methylamine, Py=pyridine) and trans,trans,trans‐[Pt(N3)2(OH)2(MA)(Tz)] ( 2 ; Tz=thiazole), and interpret their photophysical properties by TD‐DFT modelling. The orientation of the azido groups is highly dependent on H bonding and crystal packing, as shown by polymorphs 1 p and 1 q . Complexes 1 and 2 are stable in the dark towards hydrolysis and glutathione reduction, but undergo rapid photoreduction with UVA or blue light with minimal amine photodissociation. They are over an order of magnitude more potent towards HaCaT keratinocytes, A2780 ovarian, and OE19 oesophageal carcinoma cells than cisplatin and show particular potency towards cisplatin‐resistant human ovarian cancer cells (A2780cis). Analysis of binding to calf‐thymus (CT), plasmids, oligonucleotide DNA and individual nucleotides reveals that photoactivated 1 and 2 form both mono‐ and bifunctional DNA lesions, with preference for G and C, similar to transplatin, but with significantly larger unwinding angles and a higher percentage of interstrand cross‐links, with evidence for DNA strand cross‐linking further supported by a comet assay. DNA lesions of 1 and 2 on a 50 bp duplex were not recognised by HMGB1 protein, in contrast to cisplatin‐type lesions. The photo‐induced platination reactions of DNA by 1 and 2 show similarities with the products of the dark reactions of the PtII compounds trans‐[PtCl2(MA)(Py)] ( 5 ) and trans‐[PtCl2(MA)(Tz)] ( 6 ). Following photoactivation, complex 2 reacted most rapidly with CT DNA, followed by 1 , whereas the dark reactions of 5 and 6 with DNA were comparatively slow. Complexes 1 and 2 can therefore give rapid potent photocytotoxicity and novel DNA lesions in cancer cells, with no activity in the absence of irradiation. 相似文献
5.
Liang He Dr. Si‐Yan Liao Dr. Cai‐Ping Tan Rui‐Rong Ye Yu‐Wen Xu Meng Zhao Prof. Liang‐Nian Ji Prof. Dr. Zong‐Wan Mao 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(36):12152-12160
A series of RuII–arene complexes ( 1 – 6 ) of the general formula [(η6‐arene)Ru(L)Cl]PF6 (arene=benzene or p‐cymene; L=bidentate β‐carboline derivative, an indole alkaloid with potential cyclin‐dependent kinases (CDKs) inhibitory activities) is reported. All the complexes were fully characterized by classical analytical methods, and three were characterized by X‐ray crystallography. Hydrolytic studies show that β‐carboline ligands play a vital role in their aqueous behaviour. These complexes are highly active in vitro, with the most active complex 6 displaying a 3‐ to 12‐fold higher anticancer activity than cisplatin against several cancer cell lines. Interestingly, the complexes are able to overcome cross‐resistance to cisplatin, and show much lower cytotoxicity against normal cells. Complexes 1 – 6 may directly target CDK1, because they can block cells in the G2M phase, down‐regulate the expression of CDK1 and cyclin B1, and inhibit CDK1/cyclin B in vitro. Further mechanism studies show that the complexes can effectively induce apoptosis through mitochondrial‐related pathways and intracellular reactive oxygen species (ROS) elevation. 相似文献
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Dani Peri Sigalit Meker Michal Shavit Edit Y. Tshuva Dr. 《Chemistry (Weinheim an der Bergstrasse, Germany)》2009,15(10):2403-2415
Carefully design your ligand! A new family of highly cytotoxic TiIV complexes demonstrates strong dependence of activity on the particular ligand employed, in which small structural modifications dramatically affect both hydrolytic behavior and biological activity (see picture). Different structure‐dependence patterns are observed for hydrolysis and cytotoxicity, which are, nonetheless, strongly related.
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Sowmya Padejjar Vasantha Boja Poojary Revanasiddappa Bistuvalli Chandrashekarappa 《中国化学会会志》2019,66(6):638-650
In view of developing novel bioactive compounds, a series of 2‐(5‐[2‐methyl‐6‐arylpyridin‐3‐yl]‐1,3,4‐oxadiazol‐2‐ylthio)‐1‐arylethanones (6a–n) were designed and synthesized in good yield. Novel compounds were evaluated for their antibacterial and anti‐inflammatory activities. All synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus, Bascillus subtilis, Eschericia coli, and Pseudomonas aeruginosa strains. Compounds 6a , 6b , 6c , 6h , and 6i displayed the highest antibacterial activity with minimal inhibitory concentration (MIC) values ranging from 6.25–12.5 μg/mL in comparison with the standard Ciprofloxacin. The results of anti‐inflammatory activity of carrageenan‐induced footpad edema assay indicated that tested compounds exhibited remarkable anti‐inflammatory activity with percentage of inhibition of 63.9–70.1% (potency 96.8–106.20% of indomethacin activity) after 3 hr. Particularly, 6c – e and 6j – l were found to be excellent inhibitors of inflammation, with potential higher than that of the standard, Indomethacin. 相似文献
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Potent Anticancer Activity and Possible Low Toxicity of Platinum(II) Complexes with Functionalized 1,1‐Cyclobutanedicarboxylate as a Leaving Ligand 下载免费PDF全文
Jian Zhao Prof. Dr. Shaohua Gou Fengfan Liu 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(46):15216-15225
Two platinum(II) complexes, DN603 and DN604, were designed and prepared by using 3‐oxocyclobutane‐1,1‐dicarboxylate as a ligand. The compounds were prepared according to the concept that incorporation of a functionalized moiety in the leaving ligand that did not affect its coordination bonding to the metal atom would play a key role in the anticancer activity of the resulting platinum complex. The newly prepared compounds were found to show potent in vitro anticancer activity comparable to cisplatin and oxaliplatin; especially DN604, which exhibited low acute toxicity similar to carboplatin, and presented acceptable solubility and stability in water. Chemical and biological results indicated that the functionalized moiety, uncoordinated, led to potent anticancer activity and low apparent toxicity of the platinum complexes by affecting the kinetic properties of the compounds. 相似文献
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Frontispiece: Core‐Scaffold‐Inspired Asymmetric Synthesis of Polysubstituted Chiral Hexahydropyridazines that Potently Inhibit Breast Cancer Cell Proliferation by Inducing Apoptosis 下载免费PDF全文
Dr. Hai‐Jun Leng Dr. Fu Peng Dr. Sarah Zingales Dr. Wei Huang Dr. Biao Wang Dr. Qian Zhao Dr. Rui Zhou Prof. Gu He Prof. Cheng Peng Prof. Bo Han 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(50)
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Corentin Cruch Sayak Gupta Jeremy Kodanko Shawn K. Collins 《Molecules (Basel, Switzerland)》2022,27(12)
A series of copper-based photocatalysts of the type Cu(NN)(BINAP)BF4 were synthesized bearing π-extended diimine ligands. Their behavior in several photocatalytic processes were evaluated and revealed acceptable levels of activity in an SET process, but negligible activity in PCET or ET processes. Suitable activity in ET processes could be restored through modification of the ligand. The BINAP-derived complexes were then evaluated for activity against triple-negative breast cancer cell lines. Controls indicated that copper complexes, and not their ligands, were responsible for activity. Encouraging activity was displayed by a homoleptic complex Cu(dppz)2BF4. 相似文献
11.
Sandra Fernandes Shea T. Meyer Jigisha P. Shah Arijit A. Adhikari William G. Kerr John D. Chisholm 《Molecules (Basel, Switzerland)》2022,27(23)
Inhibition of phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP) with small molecule inhibitors leads to apoptosis in tumor cells. Inhibitors that target both SHIP1 and SHIP2 (pan-SHIP1/2 inhibitors) may have benefits in these areas since paralog compensation is not possible when both SHIP paralogs are being inhibited. A series of tryptamine-based pan-SHIP1/2 inhibitors have been synthesized and evaluated for their ability to inhibit the SHIP paralogs. The most active compounds were also evaluated for their effects on cancer cell lines. 相似文献
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Core‐Scaffold‐Inspired Asymmetric Synthesis of Polysubstituted Chiral Hexahydropyridazines that Potently Inhibit Breast Cancer Cell Proliferation by Inducing Apoptosis 下载免费PDF全文
Dr. Hai‐Jun Leng Dr. Fu Peng Dr. Sarah Zingales Dr. Wei Huang Dr. Biao Wang Dr. Qian Zhao Dr. Rui Zhou Prof. Gu He Prof. Cheng Peng Prof. Bo Han 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(50):18100-18108
The highly enantioselective preparation of pharmacologically interesting hexahydropyridazine derivatives based on a multicomponent cascade reaction is described. This one‐pot approach utilizes an organocatalytic Michael reaction followed by intermolecular α‐amination and intramolecular hemiaminalization to yield a chiral pyridazine backbone with contiguous stereogenic centers and multiple functional groups in good yield and with high stereoselectivity. Compounds synthesized by this method potently inhibited proliferation of MCF‐7 breast cancer cells. Mechanistic studies suggest that compound 5 c exerts these anticancer effects by inducing apoptosis through extracellular signal related kinase (ERK)‐ and poly(adenosine diphosphate ribose) polymerase (PARP)‐regulated pathways, as well as mitochondrial pathways. 相似文献
13.
Stereoselective Synthesis of the Halaven C14–C26 Fragment from D‐Quinic Acid: Crystallization‐Induced Diastereoselective Transformation of an α‐Methyl Nitrile 下载免费PDF全文
Francis Belanger Dr. Charles E. Chase Dr. Atsushi Endo Dr. Francis G. Fang Dr. Jing Li Steven R. Mathieu Dr. Annie Z. Wilcoxen Huiming Zhang 《Angewandte Chemie (International ed. in English)》2015,54(17):5108-5111
Crystallization‐induced diastereoselective transformation (CIDT) of an α‐methyl nitrile completes an entirely non‐chromatographic synthesis of the halichondrin B C14–C26 stereochemical array. The requisite α‐methyl nitrile substrate is derived from D ‐quinic acid through a series of substrate‐controlled stereoselective reactions via a number of crystalline intermediates that benefit from a rigid polycyclic template. Therefore, all four stereogenic centers in the Halaven C14–C26 fragment were derived from the single chiral source D ‐quinic acid. 相似文献
14.
Humaira Parveen Meshari A. Alsharif Mohammed I. Alahmdi Sayeed Mukhtar Amir Azam 《应用有机金属化学》2018,32(4)
Some novel pyrimidine‐based ferrocenyl substituted organometallic compounds were synthesized via multistep reactions, well characterized by different spectroscopic techniques and elemental analyses and evaluated for in vitro antiprotozoal susceptibility against HM1: IMSS strain of Entamoeba histolytica. The results of antiprotozoal susceptibility unveiled these compounds, as new leads in protozoal chemotherapy as most of the organometallics displayed an exceptionally higher antiamoebic activity (IC50 = 0.055 μM ‐ 0.815 μM) than the reference drug metronidazole which gave IC50 (50% inhibitory concentration) value 1.781 μM in our experiments, concluding that newly synthesized organometallic compounds have potential to be employed as effective antiamoebic agents and these organometallics can be very useful for further optimization work on amoebic chemotherapy. 相似文献
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Paolo Sanna Antonio Carta Laura Gherardini Mohammad Esmail Rahbar Nikookar 《ChemInform》2002,33(45):221-221
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Dr. Alessandro Barge Marina Caporaso Prof. Giancarlo Cravotto Dr. Katia Martina Dr. Paolo Tosco Prof. Silvio Aime Dr. Carla Carrera Dr. Eliana Gianolio Dr. Giorgio Pariani Dr. Davide Corpillo 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(36):12086-12092
We report the synthesis and characterization of a water‐soluble, star‐shaped macromolecular platform consisting of eight β‐cyclodextrin (β‐CD) units anchored to the narrower rim of a γ‐CD core through bis(triazolyl)alkyl spacers. The efficient synthetic protocol is based on the microwave (MW)‐promoted Cu‐catalyzed 1,3‐dipolar cycloaddition of CD monoazides to CD monoacetylenes. The ligand‐hosting capability of the construct has been assessed by relaxometric titration and nuclear magnetic relaxation dispersion (NMRD) profiling, which showed it to be good, and this was supported by molecular dynamics simulations. To demonstrate the feasibility of obtaining supramolecular structures with high hosting ability, we designed a dimeric platform, formed by joining two nonamers through the γ‐CD cores through a bis(lithocholic acid) linker. With a view to the potential biological applications, cytotoxicity and extent of binding to human serum albumin were assessed. The properties of this dendrimeric multicarrier make it suitable for pharmaceutical and diagnostic purposes, ranging from targeted drug delivery to molecular imaging. 相似文献
20.
Heteropentanuclear Oxalato‐Bridged nd–4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis,Crystal Structures,Aqueous Stability and Antiproliferative Activity 下载免费PDF全文
Dr. Paul‐Steffen Kuhn B. Sc. Laura Cremer Dr. Anatolie Gavriluta Dr. Katarina K. Jovanović Dr. Lana Filipović Dr. Alfred A. Hummer Dr. Gabriel E. Büchel Dr. Biljana P. Dojčinović Dr. Samuel M. Meier Prof. Dr. Annette Rompel Dr. Siniša Radulović Dr. Jean Bernard Tommasino Dr. Dominique Luneau Prof. Dr. Vladimir B. Arion 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(39):13703-13713
A series of heteropentanuclear oxalate‐bridged Ru(NO)‐Ln (4d–4f) metal complexes of the general formula (nBu4N)5[Ln{RuCl3(μ‐ox)(NO)}4], where Ln=Y ( 2 ), Gd ( 3 ), Tb ( 4 ), Dy ( 5 ) and ox=oxalate anion, were obtained by treatment of (nBu4N)2[RuCl3(ox)(NO)] ( 1 ) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1 , 2 , and 5 were in addition analyzed by X‐ray crystallography, 1 by Ru K‐edge XAS and 1 and 2 by 13C NMR spectroscopy. X‐ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)]2? are coordinated to YIII and DyIII, respectively, with formation of [Ln{RuCl3(μ‐ox)(NO)}4]5? (Ln=Y, Dy). While YIII is eight‐coordinate in 2 , DyIII is nine‐coordinate in 5 , with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu4N+ ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium‐lanthanide complexes 2 – 5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC‐5) and compared with those obtained for the previously reported Os(NO)‐Ln (5d–4f) analogues (nBu4N)5[Ln{OsCl3(ox)(NO)}4] (Ln=Y ( 6 ), Gd ( 7 ), Tb ( 8 ), Dy ( 9 )). Complexes 2 – 5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d–4f metal complexes 6 – 9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4 μM was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP‐MS data, indicating five‐ to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells. 相似文献