Sajid M

References (4)

Title : Synthesis, in vitro biological screening and docking study of benzo[d]oxazole bis Schiff base derivatives as a potent anti-Alzheimer agent - Taha_2022_J.Biomol.Struct.Dyn__1
Author(s) : Taha M , Rahim F , Zaman K , Anouar EH , Uddin N , Nawaz F , Sajid M , Khan KM , Shah AA , Wadood A , Rehman AU , Alhibshi AH
Ref : J Biomol Struct Dyn , :1 , 2022
Abstract : We have synthesized benzo[d]oxazole derivatives (1-21) through a multistep reaction. Alteration in the structure of derivatives was brought in the last step via using various substituted aromatic aldehydes. In search of an anti-Alzheimer agent, all derivatives were evaluated against acetylcholinesterase and butyrylcholinesterase enzyme under positive control of standard drug donepezil (IC(50) = 0.016 +/- 0.12 and 4.5 +/- 0.11 microM) respectively. In case of acetylcholinesterase enzyme inhibition, derivatives 8, 9 and 18 (IC(50) = 0.50 +/- 0.01, 0.90 +/- 0.05 and 0.3 +/- 0.05 microM) showed very promising inhibitory potentials. While in case of butyrylcholinesterase enzyme inhibition, most of the derivatives like 6, 8, 9, 13, 15, 18 and 19 (IC(50) = 2.70 +/- 0.10, 2.60 +/- 0.10, 2.20 +/- 0.10, 4.25 +/- 0.10, 3.30 +/- 0.10, 0.96 +/- 0.05 and 3.20 +/- 0.10 microM) displayed better inhibitory potential than donepezil. Moreover, derivative 18 is the most potent one among the series in both inhibitions. The binding interaction of derivatives with the active gorge of the enzyme was confirmed via a docking study. Furthermore, the binding interaction between derivatives and the active site of enzymes was correlated through the SAR study. Structures of all derivatives were confirmed through spectroscopic techniques such as (1)H-NMR, (13)C-NMR and HREI-MS, respectively.Communicated by Ramaswamy H. Sarma.
ESTHER : Taha_2022_J.Biomol.Struct.Dyn__1
PubMedSearch : Taha_2022_J.Biomol.Struct.Dyn__1
PubMedID: 34989316

Title : Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases - Rahim_2016_Bioorg.Chem_68_30
Author(s) : Rahim F , Ullah H , Taha M , Wadood A , Javed MT , Rehman W , Nawaz M , Ashraf M , Ali M , Sajid M , Ali F , Khan MN , Khan KM
Ref : Bioorg Chem , 68 :30 , 2016
Abstract : To discover multifunctional agents for the treatment of Alzheimer's disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC50 values 4.12+/-0.01, 8.12+/-0.01 and 8.41+/-0.06muM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC50=0.85+/-0.0001muM). Three compounds 13, 24 and 3 having IC50 values 6.51+/-0.01, 9.22+/-0.07 and 37.82+/-0.14muM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC50=0.04+/-0.0001muM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed.
ESTHER : Rahim_2016_Bioorg.Chem_68_30
PubMedSearch : Rahim_2016_Bioorg.Chem_68_30
PubMedID: 27441832

Title : The oligopeptidase B of Leishmania regulates parasite enolase and immune evasion - Swenerton_2011_J.Biol.Chem_286_429
Author(s) : Swenerton RK , Zhang S , Sajid M , Medzihradszky KF , Craik CS , Kelly BL , McKerrow JH
Ref : Journal of Biological Chemistry , 286 :429 , 2011
Abstract : Proteases are a ubiquitous group of enzymes that play key roles in the life cycle of parasites, in the host-parasite relationship, and in the pathogenesis of parasitic diseases. Furthermore, proteases are targets for the development of new anti-parasitic therapy. Protozoan parasites like Leishmania predominantly express Clan CA cysteine proteases for key life cycle functions. It was therefore unexpected to find a high level of serine protease activity expressed by Leishmania donovani. Purification of this activity followed by mass spectrometry identified oligopeptidase B (OPB; Clan SC, family S9A) as the responsible enzyme. This was confirmed by gene knock-out of OPB, which resulted in the disappearance of the detected serine protease activity of Leishmania extracts. To delineate the specific role of OPB in parasite physiology, proteomic analysis was carried out on OPB(-/-) versus wild type parasites. Four protein species were significantly elevated in OPB(-/-) parasites, and all four were identified by mass spectrometry as enolase. This increased enolase was enzymatically inactive and associated with the parasite membrane. Aside from its classic role in carbohydrate metabolism, enolase was recently found to localize to membranes, where it binds host plasminogen and functions as a virulence factor for several pathogens. As expected, there was a striking alteration in macrophage responses to Leishmania when OPB was deleted. Whereas wild type parasites elicited little, if any, response from infected macrophages, OPB(-/-) parasites induced a massive up-regulation in gene transcription. Additionally, these OPB(-/-) parasites displayed decreased virulence in the murine footpad infection model.
ESTHER : Swenerton_2011_J.Biol.Chem_286_429
PubMedSearch : Swenerton_2011_J.Biol.Chem_286_429
PubMedID: 20961853
Gene_locus related to this paper: leima-OPB

Title : The genome of the blood fluke Schistosoma mansoni - Berriman_2009_Nature_460_352
Author(s) : Berriman M , Haas BJ , LoVerde PT , Wilson RA , Dillon GP , Cerqueira GC , Mashiyama ST , Al-Lazikani B , Andrade LF , Ashton PD , Aslett MA , Bartholomeu DC , Blandin G , Caffrey CR , Coghlan A , Coulson R , Day TA , Delcher A , DeMarco R , Djikeng A , Eyre T , Gamble JA , Ghedin E , Gu Y , Hertz-Fowler C , Hirai H , Hirai Y , Houston R , Ivens A , Johnston DA , Lacerda D , Macedo CD , McVeigh P , Ning Z , Oliveira G , Overington JP , Parkhill J , Pertea M , Pierce RJ , Protasio AV , Quail MA , Rajandream MA , Rogers J , Sajid M , Salzberg SL , Stanke M , Tivey AR , White O , Williams DL , Wortman J , Wu W , Zamanian M , Zerlotini A , Fraser-Liggett CM , Barrell BG , El-Sayed NM
Ref : Nature , 460 :352 , 2009
Abstract : Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.
ESTHER : Berriman_2009_Nature_460_352
PubMedSearch : Berriman_2009_Nature_460_352
PubMedID: 19606141
Gene_locus related to this paper: schma-ACHE1 , schma-ACHE2 , schma-c4qb79 , schma-c4qmk4 , schma-g4v9h7 , schma-BCHE , schma-g4vmf3