Ashraf A

References (4)

Title : Experimental and Theoretical Biological Probing of Schiff Bases as Esterase Inhibitors: Structural, Spectral and Molecular Insights - Raza_2023_Molecules_28_5703
Author(s) : Raza MA , Mumtaz MW , Ozturk S , Latif M , Aisha , Ashraf A , Dege N , Dogan OE , Agar E , Rehman SU , Noor A
Ref : Molecules , 28 :5703 , 2023
Abstract : The present study was designed to evaluate the in vitro and in silico potential of the Schiff bases (Z)-4-ethoxy-N-((5-nitrothiophen-2-yl)methylene)benzenamine (1) and (Z)-2,4-diiodo-6-((2-methyl-3-nitrophenylimino)methyl)phenol (2). These Schiff bases were synthesized according to a reported method using ethanol as a solvent, and each reaction was monitored on a TLC until completion of the reaction. The structures of both compounds were elucidated using spectroscopic techniques such as UV-Vis, FTIR, (1)H NMR and (13)C NMR. Molecular structure was determined using single-crystal XRD, which revealed that compounds 1 and 2 were monoclinic and triclinic, respectively. Hirshfeld surface analysis (HS) and 2D fingerprint plots were used to determine the intermolecular interactions along the contact contribution in the crystalline molecules. The structures of both compounds were optimized through a hybrid functional method B3LYP using the 6-31G(d,p) basis set, and various structural parameters were studied. The experimental and theoretical parameters (bond angle and bond length) of the compounds were compared with each other and are in close agreement. The in vitro esterase potential of the synthesized compounds was checked using a spectrophotometric model, while in silico molecular docking studies were performed with AutoDock against two enzymes of the esterase family. The docking studies and the in vitro assessment predicted that such molecules could be used as enzyme inhibitors against the tested enzymes: acetylcholine esterase (AChE) and butyrylcholine esterase (BChE).
ESTHER : Raza_2023_Molecules_28_5703
PubMedSearch : Raza_2023_Molecules_28_5703
PubMedID: 37570673

Title : Synthesis, biological activity and docking calculations of bis-naphthoquinone derivatives from Lawsone - Riaz_2021_Bioorg.Chem_114_105069
Author(s) : Riaz MT , Yaqub M , Shafiq Z , Ashraf A , Khalid M , Taslimi P , Tas R , Tuzun B , Gulcin I
Ref : Bioorg Chem , 114 :105069 , 2021
Abstract : Some metabolic enzyme inhibitors can be used as Multi-target-Directed-Ligands (MTDL) in Medicinal chemistry therefore, synthesis and determination of alternative inhibitors are essential. In this study, novel bis-napthoquinone derivatives (5a-o) were synthesized through a multi-component cascade reaction of two molecules of 2-hydroxy-1,4-naphthoquinone with an aromatic aldehyde in basic media using triethylamine as a catalyst. This novel heterocyclic derivatives (5a-o) are applied to inhibit the carbonic anhydrase (hCA I and hCA II) isoform in low levels of nano molecules with Ki values exist between 4.62 +/- 1.01 to 70.45 +/- 9.03 nM for hCA I and for hCA II which is physiologically dominant K(i)s values are in the range of 5.61 +/- 1.04 to 73.26 +/- 10.25 nM. Further these novel derivatives (5a-o) efficiently inhibit AChE with Ki values in the range of 0.13 +/- 0.02 to 3.16 +/- 0.56 nM. The compounds are also applied for BChE with Ki values varying between 0.50 +/- 0.10 to 9.23 +/- 1.15 nM. For alpha-glycosidase, the most efficient Ki values of 5e and 5f are 76.14 +/- 9.60 and 95.27 +/- 12.55 nM respectively. Finally, molecular docking calculations against enzymes (acetylcholinesterase, butyrylcholinesterase, and the human carbonic anhydrase I and II) are compared using biological activities of heterocyclic derivatives. After these calculations, an ADME/T analysis is performed to study the future medicinal use of heterocyclic derivatives from lawsone.
ESTHER : Riaz_2021_Bioorg.Chem_114_105069
PubMedSearch : Riaz_2021_Bioorg.Chem_114_105069
PubMedID: 34134033

Title : In silico and BSA binding study of some new biological analogs of 1,2,4-triazolependant with azinane through microwave and conventional synthesis - Virk_2018_Pak.J.Pharm.Sci_31_2645
Author(s) : Virk NA , Rehman A , Abbasi MA , Siddiqui SZ , Ashraf A , Lateef M , Javed H , Iqbal J , Khalid H , Khan S
Ref : Pak J Pharm Sci , 31 :2645 , 2018
Abstract : Microwave and conventional techniques were employed to synthesize a novel array of compounds 7a-g with 1,2,4-triazole and piperidine rings having great biological importance. The microwave assisted method has a better operational scope with respect to time and yield comparative to the conventional method. 1H-NMR, 13C-NMR and IR techniques were employed to justify the structure of synthesized compounds. The antioxidant, butyrylcholinesterase inhibition and urease inhibition potential of every synthesized compound was evaluated. Every member of the synthesized series was found potent against mentioned activities. Compound 7g was the most active anti-urease agent having IC50 (muM) value 16.5+/-0.09 even better than the thiourea with an IC50(muM) value of 24.3+/-0.24. The better urease inhibition potential of 7g was also elaborated and explained by docking and bovine serum albumin (BSA) binding studies.
ESTHER : Virk_2018_Pak.J.Pharm.Sci_31_2645
PubMedSearch : Virk_2018_Pak.J.Pharm.Sci_31_2645
PubMedID: 30587474

Title : The transgenic expression of LARGE exacerbates the muscle phenotype of dystroglycanopathy mice - Whitmore_2014_Hum.Mol.Genet_23_1842
Author(s) : Whitmore C , Fernandez-Fuente M , Booler H , Parr C , Kavishwar M , Ashraf A , Lacey E , Kim J , Terry R , Ackroyd MR , Wells KE , Muntoni F , Wells DJ , Brown SC
Ref : Hum Mol Genet , 23 :1842 , 2014
Abstract : Mutations in fukutin-related protein (FKRP) underlie a group of muscular dystrophies associated with the hypoglycosylation of alpha-dystroglycan (alpha-DG), a proportion of which show central nervous system involvement. Our original FKRP knock-down mouse (FKRP(KD)) replicated many of the characteristics seen in patients at the severe end of the dystroglycanopathy spectrum but died perinatally precluding its full phenotyping and use in testing potential therapies. We have now overcome this by crossing FKRP(KD) mice with those expressing Cre recombinase under the Sox1 promoter. Owing to our original targeting strategy, this has resulted in the restoration of Fkrp levels in the central nervous system but not the muscle, thereby generating a new model (FKRP(MD)) which develops a progressive muscular dystrophy resembling what is observed in limb girdle muscular dystrophy. Like-acetylglucosaminyltransferase (LARGE) is a bifunctional glycosyltransferase previously shown to hyperglycosylate alpha-DG. To investigate the therapeutic potential of LARGE up-regulation, we have now crossed the FKRP(MD) line with one overexpressing LARGE and show that, contrary to expectation, this results in a worsening of the muscle pathology implying that any future strategies based upon LARGE up-regulation require careful management.
ESTHER : Whitmore_2014_Hum.Mol.Genet_23_1842
PubMedSearch : Whitmore_2014_Hum.Mol.Genet_23_1842
PubMedID: 24234655