Faizul Hassan Nasim

Discovery of indole-based tetraarylimidazoles as potent inhibitors of urease with low antilipoxygenase activity.

A series of tetraarylimidazoles (5A-5O) were prepared by one pot four component condensation reactions of 2-arylindole-3-carbaldehydes, substituted anilines, benzil and ammonium acetate in acetic acid. The synthesized compounds exhibited potent antiurease activity with IC50 values ranging from 0.12 ± 0.06 μM to 29.12 ± 0.18 μM as compared with thiourea. However, low inhibition profiles were observed for lipoxygenase. The data show that tetraarylimidazoles containing a substituted 2-penylindole have emerged as a new class of potent inhibitors of urease enzyme.

Investigation of the effect of anti-neoplastic drugs, cyclophosphamide, cisplatin and methotrexate on the turnover kinetics of human erythrocyte acetylcholinesterase

The present work addresses the effects of three antineoplastic drugs [cyclophosphamide (CP), cisplatin (CDDP) and methotrexate (MTX) which are in current use for the treatment of various tumors] on turnover kinetics of human erythrocyte membrane‐bound acetylcholinesterase (AcChoEase, EC 3.1.1.7). It was found that CP and MTX significantly decreased kcat and ksp, whereas CDDP decreased only the kcat value, (ksp was non‐significantly affected). In light of these findings, the CP, CDDP and MTX needs particular attention in tumor therapy and their effects on turnover number must be considered at the time of administering these drugs to cancer patients.

Synthesis of novel quinoxalinone derivatives by conventional and microwave methods and assessing their biological activity

In this study, twenty-one arylaminoquinoxalinone derivatives were synthesized and their antibacterial activities against Staphylococci aureus, Pseudomonas aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Shigella pneumoniae were evaluated relative to known antibiotics; augmentin, ampicillin, and chloramphenicol. The insecticidal activities of the prepared compounds were also investigated against Tribolium castaneum using permethrin as a standard insecticide. The derivatives were synthesized using both conventional and microwave techniques. Their structures were confirmed using spectral techniques and elemental analysis.

Human erythrocyte acetylcholinesterase inhibition by cis-diamminediaquaplatinum (II): a novel kinetic approach.

The present work addresses the analyses of some novel kinetic parameters (k(t), K(v), t50, K(ir), t(c), m(c), IC50, IC99 and Ki) of human erythrocyte membrane-bound acetylcholinesterase (AChE, EC 3.1.1.7) inhibition by cis-diamminediaquaplatinum II (PDC). PDC is under a clinical trial for use as an antineoplastic drug. The authors recently reported that PDC and cisplatin have the ability to inhibit AChE activity in vitro. Therefore this study was designed to determine the estimation of time constant (k(t)), velocity constant (K(v)), 50% inhibition time (t50), inhibition rate constant (K(ir)), transition concentration (t(c)), meeting concentration (m(c)), 50% inhibition (IC50), 99% inhibition (IC99) and inhibition constant (Ki) by novel methods. The details are described in the text.

In vitro inhibition of human erythrocyte acetylcholinesterase (EC3.1.1.7) by an antineoplastic drug methotrexate

This work addresses the kinetic analysis of the interaction of methotrexate (MTX) with human erythrocyte membrane-bound acetylcholinesterase (AChE, EC 3.1. 1.7). It was found that the MTX effect was independent of time of incubation with AChE before the addition of substrate which proves its reversible action. The IC50 was determined, by three methods, to be 0.73 mM. The Michaelis-Menten constant (Ks) for the hydrolysis of acetylthiocholine iodide (ASCh) by AChE was 0.13 mM in the control system, a value decreased by 30–61% in the MTX treated systems. The Vmax was 1.27μtmole/min/mg protein for the control system while it was decreased by 44–77% in the MTX treated systems. The Linexveaver-Buck plot, Dixon plot, and their secondary replots indicated that the nature of the inhibition was of the linear mixed type, i.e. uncompetitive and noncompetitive. The values of Ki(slope) and KI(tntecept) were estimated as 1.67 and 0.34 mM, respectively.

Specific Cholinesterase Inhibitors: A Potential Tool to Assist in Management of Alzheimer Disease

Accompanying the gradual rise in the average age of the population of most industrialized countries is a regrettable escalation in individuals afflicted with progressive neurodegenerative disorders, epitomized by Alzheimers disease (AD). The development of effective new treatment strategies for AD has therefore become one of the most critical challenges in current neuroscience. Cholinesterase inhibitors (ChEIs) remain the primary therapeutic strategy for AD, and act by amplifying residual cholinergic activity, a neurotransmitter system central in cognitive processing that is reported to be depleted in the AD brain. With the recent failure of current drug classes focused towards the molecular events known to underpin AD, including the generation of amyloid-β peptide (Aβ) containing plaques and neurofibrillary tangles (hyper-phosphorylated tau). The development of new generation of cholinergic drugs has been accomplished to take advantage of the known modulatory action of the cholinergic system on Aβ, tau production as well as the maintenance synapses, which are known to be lost in AD. Following upon the development of acetylcholinesterase inhibitors (AChE-Is), phenserine, that additionally possessed amyloid precursor protein (APP) synthesis inhibitory actions to lower the generation of Aβ. Selective butyrylcholinesterase inhibitors (BuChE-Is), cymserine analogues, have been developed on the same chemical backbone during further anti-AD research advancement. The above mentioned inhibitors retain actions on APP as well as Aβ and amplify central cholinergic actions without the classical dose-limiting adverse effect profile; therefore, these current BuChE-Is are now moving into AD clinical trials.

Nickel Metal Uptake and Metal-Specific Stress Alleviation in a Perennial Desert Grass Cenchrus ciliaris

Associations of Vesicular Arbuscular Mycorrhizal Fungi (VAMF) with plant roots are known to function from Stress Alleviation to Bioremediation in metal polluted soils. We have studied uptake and accumulation of Nickel metal in a perennial grass, Cenchrus ciliaris, from Cholistan desert in the presence or the absence of mycorrhizal colonization of its roots by a fungus Glomous mosseae. Our results show that Cenchrus ciliaris has a tendency to absorb and tolerate the Nickel metal present in the contaminated soils and its shoots accumulate more Nickel than its roots. Introduction of Nickel in the plant rhizosphere generates stress that at some concentrations creates anatomical changes both at macro and microscopic levels. Such concentrations also adversely affect fungal colonization. Nature and extent of the stress directly correlate with the concentration of the Nickel metal in the soil. Metal exposure alone or in combination with the mycorrhiza produces specific changes in some enzyme activities both in the root and the shoot tissues suggesting that these changes are involved in progression/regression of the metal-specific stress. While Glomous mosseae association is not required for Nickel uptake and accumulation by Cenchrus ciliaris, it appears to be helpful in alleviating the stress exerted by the presence of this metal in soil. We conclude that the perennial desert grass Cenchrus ciliaris is capable of mobilizing and up taking Nickel metal from soil, its transportation from roots to shoots and is equipped with the machinery that helps tolerate the metal-specific stress to some extent.