Synthesis, biological evaluation and DFT calculation of novel pyrazole and pyrimidine derivatives

Farag, Ahmad M.; Fahim, Asmaa M.

doi:10.1016/j.molstruc.2018.11.008

Cited by 72 publications

(39 citation statements)

References 56 publications

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“…To understand electronic communication in L 1 – L 4 , theoretical calculations have been performed using DFT calculation. With reference to frontier molecular orbital theory, the energy of HOMO and LUMO orbital levels are very significant factors that affected bioactivity and play a vital role in various pharmacological processes . The energy and geometry optimization was accomplished using Gaussian 09 program .…”

Section: Resultsmentioning

confidence: 99%

“…From L 1 to L 4 , the lowest band gap is observed in the case of L 1 while the highest was found in the case of L 4 , which means that electronic communications between HOMO and LUMO orbitals of L 1 will be easier in comparison to L 4 . Consequently, low HOMO‐LUMO energy gap leads to more stabilization of the LUMO orbital due to the strong electron accepting ability of the electron‐acceptor group of molecules which further effects its biological activity . Thus, to some extent, the DFT calculation can explain the lowest band gap of L 1 which allows its strongest interaction with investigated proteins and DNA.…”

Section: Resultsmentioning

confidence: 99%

“…Consequently, low HOMO-LUMO energy gap leads to more stabilization of the LUMO orbital due to the strong electron accepting ability of the electron-acceptor group of molecules which further effects its biological activity. [43] Thus, to some extent, the DFT calculation can explain the lowest band gap of L 1 which allows its strongest interaction with investigated proteins and DNA.…”

Section: Density Functional Calculationmentioning

confidence: 96%

“…orbital theory, the energy of HOMO and LUMO orbital levels are very significant factors that affected bioactivity and play a vital role in various pharmacological processes. [43,44] The energy and geometry optimization was accomplished using Gaussian 09 program. [45] 6-31G basis set has been used throughout the calculation for carbon (C), hydrogen (H), oxygen (O) and nitrogen (N) atoms.…”

Section: Density Functional Calculationmentioning

confidence: 99%

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Design and Construction of Aroyl‐Hydrazone Derivatives: Synthesis, Crystal Structure, Molecular Docking and Their Biological Activities

Kumari

Ansari

Kumar

et al. 2019

Chemistry & Biodiversity

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Here, we report the synthesis and characterization of four new aroyl‐hydrazone derivatives L1–L4, and their structural as well as biological activities have been explored. In addition to docking with bovine serum albumin (BSA) and duplex DNA, the experimental results demonstrate the effective binding of L1–L4 with BSA protein and calf thymus DNA (ct‐DNA) which is in agreement with the docking results. Further biological activities of L1–L4 have been examined through molecular docking with different proteins which are involved in the propagation of viral or cancer diseases. L1 shows best binding affinity with influenza A virus polymerase PB2 subunit (2VY7) with binding energy −11.42 kcal/mol and inhibition constant 4.23 nm, whereas L2 strongly bind with the hepatitis C virus NS5B polymerase (2WCX) with binding energy −10.47 kcal/mol and inhibition constant 21.06 nm. Ligand L3 binds strongly with TGF‐beta receptor 1 (3FAA) and L4 with cancer‐related EphA2 protein kinases (1MQB) with binding energy −10.61 kcal/mol, −10.02 kcal/mol and inhibition constant 16.67 nm and 45.41 nm, respectively. The binding energies of L1–L4 are comparable with binding energies of their proven inhibitors. L1, L3 and L4 can be considered as both 3FAA and 1MQB dual targeting anticancer agents, while L1 and L3 are both 2VY7 and 2WCX dual targeting antiviral agents. On the other side, L2 and L4 target only one virus related target (2WCX). Furthermore, the geometry optimizations of L1–L4 were performed via density functional theory (DFT). Moreover, all four ligands (L1–L4) were characterized by NMR, FT‐IR, ESI‐MS, elemental analysis and their molecular structures were validated by single crystal X‐ray diffraction studies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Density Functional Calculationmentioning

confidence: 96%

Section: Density Functional Calculationmentioning

confidence: 99%

See 2 more Smart Citations

Design and Construction of Aroyl‐Hydrazone Derivatives: Synthesis, Crystal Structure, Molecular Docking and Their Biological Activities

Kumari

Ansari

Kumar

et al. 2019

Chemistry & Biodiversity

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“…So far, different synthetic routes towards pyrazolo [1,5-a]pyrimidines have been reported. These methods have been mainly included the condensation of 3-aminopyrazoles with 1,3-bis electrophilic substrates [51][52][53][54][55][56][57][58][59] , 1,2-allenic lactones 60 , β-halovinyl aldehyde 61 , and activated alkynes 62,63 .…”

mentioning

confidence: 99%

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

Peytam

Adib

Shourgeshty

et al. 2020

Sci Rep

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In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC 50 values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC 50 = 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones. Recently, the world health organization (WHO) has identified the diabetes mellitus (DM) as a critical health challenge in the 21st century. The prevalence of diabetes has been increasing at alarming rate over the past three decades. This metabolic disorder, characterized by chronic hyperglycemia, leads to further severe damages like abnormally great thrust, excessive appetite, overweigh, blindness, excessive urination, cardiovascular complications, as well as renal and neurodegenerative diseases 1-6. There are three main diabetes types among which type 2 or non-insulin dependent (T2DM) is the most common one, mainly treated by controlling the digestive enzyme activities such as α-glucosidase 7-9. α-Glucosidase, found in the brush-border surface membrane of intestinal cells, plays catalyzing role in the carbohydrate digestion process by which the postprandial blood glucose levels increases. Preventing the glucose release in the bloodstream, the α-glucosidase inhibitors control T2DM 10. Additionally, this enzyme has a pivotal role in the biosynthesis of glycoprotein, therefore, its inhibitors have possessed anticancer, antitumor, antiviral, and immunoregulatory properties 11-15. Acrabose, miglitol, voglibose, and deoxynojirimycin have clinically been used to restrict the α-glucosidase activity 16. Considering the side effects and absorption problems associated with these drugs, new scaffolds should be synthesized and evaluated by medicinal chemists to extend the library of compounds 17-25. Pyrazoles are common structural motif in numerous drugs 26 and biologically active compounds showing activities such as anti-cancer 27,28 , anti-inflammatory 29 , anti-hypertensive 30 , cannabinoid receptor antagonist 31 , dopaminergic receptor antagonist 32 , and α-glucosidase inhibitors 33. Pyrazoles have been used to synthesize

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Synthesis, characterization, thermal studies, electrochemical behavior, antimicrobial, docking studies, and computational simulation of triazole‐thiol metal complexes

Fahim

Magar

Ayoub

2022

Applied Organom Chemis

Self Cite

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In this study, we elucidate the structure and molecular properties of triazole‐thiol derivative (HL) which is confirmed via B3LYP/6‐31G(d) for DFT and HF basis set. Triazole‐thiol (HL) was conjugated with several metal ions to afford stable metal complexes. Consequently, confirmed via intensive physicochemical analysis including FT‐IR spectra, elemental analysis, electronic, 1H‐NMR, TGA, and DTA. The explanation of the thermal cracking of these metal complexes has been estimated. The FT‐IR of these complexes indicated the presence of triazole‐thiol ligand (HL) as chelated coordinated through the N atom of amino group and S atom of SH moiety. Furthermore, Fe(III) complex and Ni(II) adopt octahedral stereochemistry, while the Cu(II) complex is trigonal bipyramidal, and Cd(II) complex is square planar. Thermal investigation maintained the chemical formulation of these metal complexes and exhibited that they decompose in many stages dependent on the kind of ligand and geometry of complexes. Moreover, the HL and metal complexes were exhibited antimicrobial evaluation against bacterial and fungal strains and showed higher activity comparable HL. Additionally, the theoretical docking stimulation of the ligand HL and metal complexes with different proteins showed different in energy affinity with shortage bond length with metal complexes and confirmed the experimental biological results. Eventually, the electrochemical features were explored utilizing cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS).

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Synthesis, biological evaluation and DFT calculation of novel pyrazole and pyrimidine derivatives

Cited by 72 publications

References 56 publications

Design and Construction of Aroyl‐Hydrazone Derivatives: Synthesis, Crystal Structure, Molecular Docking and Their Biological Activities

Design and Construction of Aroyl‐Hydrazone Derivatives: Synthesis, Crystal Structure, Molecular Docking and Their Biological Activities

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

Synthesis, characterization, thermal studies, electrochemical behavior, antimicrobial, docking studies, and computational simulation of triazole‐thiol metal complexes

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