15029-30-8Relevant articles and documents
Part 1: Experimental and theoretical studies of 2-cyano-2-isonitroso-N- piperidynylacetamide (HPiPCO), 2-cyano-2-isonitroso-N-morpholylacetamide (HMCO) and their Pt- and Pd-complexes
Ratcliff, Jessica,Kuduk-Jaworska, Janina,Chojnacki, Henryk,Nemykin, Victor,Gerasimchuk, Nikolay
, p. 1 - 11 (2012)
The reaction between substituted cyan-acetamides NC-CH2-C(O)X (X = N-piperidyne or N-morpholyl residues) and gaseous methylnitrite CH 3ONO in isopropanol at room temperature in the presence of a base within minutes leads to colorless cyanoximes 2-cyano-2-isonitroso-N- piperidynylacetamide (further as HPiPCO), and 2-cyano-2-isonitroso-N- morpholylacetamide (HMCO) in 70-90% yield. The deprotonation of HPiPCO and HMCO with a base such as NaOEt affords anionic Na-salts, bright-yellow in color originated from n → π* transitions in the nitroso-chromophore. Anionic cyanoximates react with aqueous solutions of K 2MCl4 (M = Pd, Pt) to form yellow-orange PdL2 and dark blue-green polymeric [PtL2]n (L = PiPCO -, MCO-), which upon treatment with DMSO or DMF breaks down to pale-yellow monomeric PtL2. Synthesized metal complexes were characterized by spectroscopic methods (IR, UV-Vis), measurement of the electric conductivity and the X-ray analysis. Both PdL2 and PtL2 exhibit non-electrolyte behavior in DMSO and DMF. Crystal structures of Pd(PiPCO)2 and Pt(PiPCO)2 were determined and revealed the formation of the cis-complexes with nearly planar geometry around the metal core and an adoption of the cis-anti configuration by anions, in contrast to the trans-anti geometry in structures of uncomplexed HPiPCO and HMCO. Ab initio calculations were performed for all six compounds: two cyanoxime ligands and four Pd and Pt metal complexes. A very satisfactory agreement between the calculated and experimental values of geometrical parameters of all evaluated compounds was attained. The electron densities, energies of HOMO and LUMO orbitals and molecular electrostatic potentials were calculated as well.
Synthesis and biological evaluation of flavone-8-acrylamide derivatives as potential multi-target-directed anti Alzheimer agents and investigation of binding mechanism with acetylcholinesterase
Shaik, Jeelan Basha,Yeggoni, Daniel Pushparaju,Kandrakonda, Yelamanda Rao,Penumala, Mohan,Zinka, Raveendra Babu,Kotapati, Kasi Viswanath,Darla, Mark Manidhar,Ampasala, Dinakara Rao,Subramanyam, Rajagopal,Amooru, Damu Gangaiah
, (2019/05/17)
In a search for novel multifunctional anti-Alzheimer agents, a congeneric set of seventeen flavone-8-acrylamide derivatives (8a─q)were synthesized and evaluated for their cholinesterase inhibitory, antioxidant, neuroprotective and modulation of Aβ aggregation activities. The target compounds showed effective and selective inhibitory activity against the AChE over BuChE. In addition, the target compounds also showed moderate anti-oxidant activity and strong neuroprotective capacities, and accelerated dosage-dependently the Aβ aggregation. Also, we presented here a complete study on the interaction of 8a, 8d, 8e, 8h and 8i with AChE. Through fluorescence emission studies, the binding sites number found to be 1, binding constants were calculated as 2.04 × 104, 2.22 × 104, 1.18 × 104, 9.8 × 103 and 3.2 × 104 M?1 and free energy change as ?5.83, ?5.91, ?5.51, ?5.41 and ?6.12 kcal M?1 at 25 °C which were well agreed with the computational calculations indicating a strong binding affinity of flavones and AChE. Furthermore, the CD studies revealed that the secondary structure of AChE became partly unfolded upon binding with 8a, 8d, 8e, 8h and 8i.
New Flavone-Cyanoacetamide Hybrids with a Combination of Cholinergic, Antioxidant, Modulation of β-Amyloid Aggregation, and Neuroprotection Properties as Innovative Multifunctional Therapeutic Candidates for Alzheimer's Disease and Unraveling Their Mechanism of Action with Acetylcholinesterase
Basha, Shaik Jeelan,Mohan, Penumala,Yeggoni, Daniel Pushparaju,Babu, Zinka Raveendra,Kumar, Palaka Bhagath,Rao, Ampasala Dinakara,Subramanyam, Rajagopal,Damu, Amooru Gangaiah
, p. 2206 - 2223 (2018/05/23)
In line with the modern multi-target-directed ligand paradigm of Alzheimer's disease (AD), a series of 19 compounds composed of flavone and cyanoacetamide groups have been synthesized and evaluated as multifunctional agents against AD. Biological evaluation demonstrated that compounds 7j, 7n, 7o, 7r, and 7s exhibited excellent inhibitory potency (AChE, IC50 of 0.271 ± 0.012 to 1.006 ± 0.075 μM) and good selectivity toward acetylcholinesterase, significant antioxidant activity, good modulation effects on self-induced Aβ aggregation, low cytotoxicity, and neuroprotection in human neuroblastoma SK-N-SH cells. Further, an inclusive study on the interaction of 7j, 7n, 7o, 7r, and 7s with AChE at physiological pH 7.2 using fluorescence, circular dichroism, and molecular docking methods suggested that these derivatives bind strongly to the peripheral anionic site of AChE mostly through hydrophobic interactions. Overall, the multifunctional profiles and strong AChE binding affinity highlight these compounds as promising prototypes for further pursuit of innovative multifunctional drugs for AD.
