16135-31-2Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel α-acyloxy carboxamides via Passerini reaction as caspase 3/7 activators
Salah Ayoup, Mohammed,Wahby, Yasmin,Abdel-Hamid, Hamida,Ramadan, El Sayed,Teleb, Mohamed,Abu-Serie, Marwa M.,Noby, Ahmed
, p. 340 - 356 (2019)
Evasion of apoptosis is a hallmark of cancer. Caspases; the key executors of apoptotic cascade are attractive targets for selective induction of apoptosis in cancer cells. Within this approach, various caspase activators were introduced as lead anticancer agents. In the current study, a new series of multifunctional Passerini products was synthesized and evaluated as potent caspase-dependent apoptotic inducers. The synthetic strategy adopted this isocyanide-based multicomponent reaction to possibly mimic the pharmacophoric features of various lead apoptotic inducers, where a series of α-acyloxy carboxamides was prepared from p-nitrophenyl isonitrile, cyclohexanone and various carboxylic acids. Accordingly, the main amide-based scaffold was decorated by substituents with varying nature and size to gain more information about structure-activity relationship. All the synthesized compounds were screened for cytotoxicity against normal human fibroblasts and their potential anticancer activities against three human cancer cell lines; MCF-7 (breast), NFS-60 (myeloid leukemia), and HepG-2 (liver) utilizing MTT assay. Among the most active compounds, 13, 21 and 22 were more potent and safer than doxorubicin with nanomolar IC50 values and promising selectivity indices. Mechanistically, 13, 21 and 22 induced apoptosis by significant caspase activation in all the screened cancer cell lines utilizing flow cytometric analysis and caspase 3/7 activation assay. Again, 13 and 21 recorded higher activation percentages than doxorubicin, while 22 showed comparable results. Apoptosis-inducing factor1 (AIF1) quantification assay declared that 13, 21 and 22 didn't mediate apoptosis through AIF1-dependent pathway (i.e. only by caspase activation). Physicochemical properties, pharmacokinetic profiles, ligand efficiency metrics and drug-likeness data of all the synthesized compounds were computationally predicted and showed that 13, 21 and 22 could be considered as drug-like candidates. Finally, selected compounds were preliminarily screened for possible antimicrobial activities searching for dual anticancer/antimicrobial agents as an advantageous approach for cancer therapy.
Microwave promoted energy-efficient N-formylation with aqueous formic acid
Bose, Ajay K.,Ganguly, Subhendu N.,Manhas, Maghar S.,Guha, Atri,Pombo-Villars, Esteban
, p. 4605 - 4607 (2006)
Microwave-induced organic reaction enhancement ('MORE') chemistry technique (open vessel; controlled microwave energy to stay below the boiling point of the reaction mixture) was used for the N-formylation of aliphatic and aromatic amines and amino heterocycles with aq formic acid (80%) on a multiple gram scale in a few minutes.
p-Nitrophenyl isocyanide
Zeller, Matthias,Hunter, Allen D.
, p. o415-o417 (2004)
Achiral p-nitrophenyl isocyanide, C7H4N 2O2, crystallizes in the orthorhombic chiral space group P212121. Attractive intermolecular interactions between the nitro O atoms and both aromatic H and nitro N atoms of neighbouring molecules are observed. The O...N interaction is surprisingly strong [N...O = 2.869 (2) A] compared with other aromatic nitro compounds.
Hydrogen bonding in aromatic formamides
Zeller, Matthias,Wilcox, Robert J.,Snyder III, Floyd G.,Seibel II, Harry A.,Takas, Nathan J.,Hunter, Allen D.
, p. 723 - 729 (2005)
The solid state structures of two p-substituted aromatic formamides have been determined. p-Nitro formamido benzene (1) crystallizes in the monoclinic space group C2/c with a = 10.9859(7), b = 10.0576(7), c = 13.0331(9) A, β = 97.148(1)° and Z = 8. p-formamido anisole (2) crystallizes in the orthorhombic space group Pna21 with a = 10.5598(7), b = 7.6553(5), c = 9.2522(6) A and Z = 4. Both compounds show hydrogen bonding in the solid state, forming infinite chains via N-H...O = C bridges. For the anisole formamide (2), the molecules exhibit in a zig-zag arrangement. The nitro compound (1) exhibits a spiral-like wavy line with a fourfold repeating unit, making it the first formamide having a chiral N-H...O bridged chain reminiscent of those found for α-helices in proteins. While the individual spirals of 1 are orientated either clockwise or counterclockwise, their orientation towards each other is random.
One-pot synthesis of 3-(2-cyanophenyl)quinazolin-4(3h)-one
Szczepankiewicz,Suwinski
, p. 809 - 810 (2000)
Anthranilonitrile reacting with formic acid at room temperature for three days gave 64% of 3-(2-cyanophenyl)quinazolin-4(3H)-one. Under similar conditions anthranilic acid, 4-nitroaniline, and 2,5-dichloroaniline were N-formylated in good yields.
Enantioselective Synthesis of Azetidines through [3 + 1]-Cycloaddition of Donor-Acceptor Aziridines with Isocyanides
Zhang, Fengcai,Sang, Xinpeng,Zhou, Yuqiao,Cao, Weidi,Feng, Xiaoming
supporting information, p. 1513 - 1517 (2022/03/01)
The enantioselective [3 + 1]-cycloaddition of racemic donor-acceptor (D-A) aziridines with isocyanides was first realized under mild reaction conditions using a chiral N,N′-dioxide/MgIIcomplex as catalyst, providing a facile route to enantioenriched exo-imido azetidines with good to excellent yield (up to 99%) and enantioselectivity (up to 94% ee). An obvious chiral amplification effect was observed in this system, and an explanation was elucidated based on the experimental investigation and X-ray crystal structure of the enantiomerically pure catalyst.
Preparation and catalytic evaluation of a palladium catalyst deposited over modified clinoptilolite (Pd&at;MCP) for chemoselective N-formylation and N-acylation of amines
Amirsoleimani, Mina,Khalilzadeh, Mohammad A.,Zareyee, Daryoush
, (2020/08/22)
Novel palladium nanoparticles stabilized by clinoptilolite as a natural inexpensive zeolite prepared and used for N-formylation and N-acylation of amines at room temperature at environmentally benign reaction conditions in good to excellent yields. Pd (II) was immobilized on the surface of clinoptilolite via facile multi-step amine functionalization to obtain a sustainable, recoverable, and highly active nano-catalyst. The structural and morphological characterizations of the catalyst carried out using XRD, FT-IR, BET and TEM techniques. Moreover, the catalyst is easily recovered using simple filtration and reused for 7 consecutive runs without any loss in activity.
Functionalizing HY zeolite with sulfonic acid, a micro-meso structure reusable catalyst for organic transformations
Tavakoli, Fatemeh,Zendehdel, Mojgan
, (2021/09/16)
A new class of sulfonic acid functionalized HY zeolite (HY-N-SA) catalyst has been prepared and characterized by some method such as XRD, FT-IR, FESEM, TEM, TGA, NH3-TPD and N2 physisorption. The result shows the micro-meso structure for catalyst without ordering in the mesophase. Then, the HY-N-SA micro-meso structure was used as an acidic catalyst to synthesize of coumarins via Pechmann reaction and facile transformation of amines to formamides under solvent-free condition. To consider the effect of acidity and kind and size of porous on the catalyst activity, this catalyst was compared with NaY-N-SA and MCM-N-SA and pure porous material (NaY and MCM-41). The significant advantages of HY-N-SA with respect to other catalysts are short reaction times, high yields, pure products, mild conditions and easy work-up. In addition, we report an original and environmentally friendly solvent-free procedure which reusability of catalyst makes this method nearly green and environmentally friendly.
Small molecule microarray identifies inhibitors of tyrosyl-DNA phosphodiesterase 1 that simultaneously access the catalytic pocket and two substrate binding sites
Zhao, Xue Zhi,Kiselev, Evgeny,Lountos, George T.,Wang, Wenjie,Tropea, Joseph E.,Needle, Danielle,Hilimire, Thomas A.,Schneekloth, John S.,Waugh, David S.,Pommier, Yves,Burke, Terrence R.
, p. 3876 - 3884 (2021/04/02)
Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a member of the phospholipase D family of enzymes, which catalyzes the removal of both 3′- and 5′-DNA phosphodiester adducts. Importantly, it is capable of reducing the anticancer effects of type I topoisomerase (TOP1) inhibitors by repairing the stalled covalent complexes of TOP1 with DNA. It achieves this by promoting the hydrolysis of the phosphodiester bond between the Y723 residue of human TOP1 and the 3′-phosphate of its DNA substrate. Blocking TDP1 function is an attractive means of enhancing the efficacy of TOP1 inhibitors and overcoming drug resistance. Previously, we reported the use of an X-ray crystallographic screen of more than 600 fragments to identify small molecule variations on phthalic acid and hydroxyquinoline motifs that bind within the TDP1 catalytic pocket. Yet, the majority of these compounds showed limited (millimolar) TDP1 inhibitory potencies. We now report examining a 21?000-member library of drug-like Small Molecules in Microarray (SMM) format for their ability to bind Alexa Fluor 647 (AF647)-labeled TDP1. The screen identified structurally similarN,2-diphenylimidazo[1,2-a]pyrazin-3-amines as TDP1 binders and catalytic inhibitors. We then explored the core heterocycle skeleton using one-pot Groebke-Blackburn-Bienayme multicomponent reactions and arrived at analogs having higher inhibitory potencies. Solving TDP1 co-crystal structures of a subset of compounds showed their binding at the TDP1 catalytic site, while mimicking substrate interactions. Although our original fragment screen differed significantly from the current microarray protocol, both methods identified ligand-protein interactions containing highly similar elements. Importantly inhibitors identified through the SMM approach show competitive inhibition against TDP1 and access the catalytic phosphate-binding pocket, while simultaneously providing extensions into both the substrate DNA and peptide-binding channels. As such, they represent a platform for further elaboration of trivalent ligands, that could serve as a new genre of potent TDP1 inhibitors.
DMF·HCl as a versatile and straightforward N- and O-formylating agent
Ramírez-Vázquez, Dulce G.,Vi?as-Bravo, Omar,Martínez-Pascual, Roxana,Pérez-Picaso, Lemuel,Castro-Cerritos, Karla Viridiana
supporting information, p. 585 - 592 (2020/11/19)
Inspired by the serendipitous isolation of N-formylpiperazines when we attempted the synthesis of a series of piperazines, we have developed a straightforward methodology for the N- and O- formylation of secondary cyclic amines, anilines and steroids, respectively. Such approach is based on the hitherto non-reported use of DMF·HCl complex, as a versatile and easily-available formylating system that can be stored without apparent loss of activity.
