Nousheen Mushtaq

Investigation of piperidine derivatives in ex vivo models of pain and platelet aggregation

Piperidine derivatives are known to exhibit analgesic activities and are likely to possess the ability to block the effects of prostaglandins through inhibition of downstream signaling pathways. The present study investigated the activity of five derivatives (PD2-6) of 4-(4′-bromophenyl)-4-piperidinol (PD1), against pain and platelet aggregation mediated by the release of prostaglandins and thromboxane A2, respectively. The results showed that compound PD1 and its two phenacyl derivatives PD3 and PD5 exhibited a highly significant analgesic effect (p < 0.01), whereas PD4 and PD6 also showed significant activity. PD3, the most active analgesic compound when docked to the opioid receptor, had interactions between the oxygen of its nitro group and the amino group of ARG 573, indicating a distance of 1.2563 Å. The antiplatelet data showed that compound PD5 (4-(4′-bromo-phenyl)-4-hydroxy-1-[2-(2″,4″-dimethoxyphenyl)-2-oxo-ethyl]-piperidinium bromide) had an IC50 = 0.06 mM, which was the most active compound, whereas PD3 was the second most active compound against platelet aggregating factor-induced aggregation with an IC50 = 80 mM. Acetyl salicylic acid (IC50 = 150 μM) was used as a positive control.

Characterisation of Plasmodium falciparum aspartic protease inhibition by piperidine derivatives

Piperidine derivatives are reported to exhibit a variety of pharmacological activities. In this article, synthesis and aspartic protease inhibitory activity of three nitrophenacyl derivatives of N-methyl-4-hydroxy piperidine are reported. Enzyme assays showed that the attachment of a nitro group in the benzene ring plays an important role in the inhibition of plasmepsin-II of Plasmodium falciparum. The compound 1-methyl-1-(4’-nitrophenacyl)-4-hydroxypiperidinium bromide (3), consisting of a nitro group at the para position, was the most active at the concentration of 1.0 µM. The activity of the compounds was evaluated through the observed orientation and diagrammatic representation of nitrophenacyl derivatives of 4-hydroxy piperidine.

Synthesis of 9-Aminoacridine Derivatives as Anti-Alzheimer Agents.

In the present study, some 9-aminoacridine derivatives have been synthesized by condensation of 9-aminoacridine with substituted phenacyl, benzoyl, and benzyl halides (RM1-RM6). Compounds were investigated for acetylcholinesterase and butyrylcholinesterase inhibition potential, considering these enzymes playing a key role in Alzheimer’s disease. All derivatives showed better inhibition of enzymes than the standard galantamine, whereas except RM4, all exhibit better results than tacrine, a well-known acridine derivative used for the treatment of Alzheimer’s disease.

(1H-Pyrrolo [2,3-B] Pyridine) 7-Azaindole as Cholinesterase/ Glycation Inhibitors.

As a part of our program to discover novel analoges of (1H-pyrrolo [2,3-b] pyridine) 7azaindole having useful biological activities, a variety of 7-azaindole analogs 1-9 with variable substituents on phenyl ring of phenacyl moiety were synthesized and evaluated for their AChE, BChE and antiglycation Inhibitory potential. Compounds 2-5 were found to Original Research Article International Journal of Biochemistry Research & Review, 4(6): 624-643, 2014 625 be AChE inhibitors with IC50 1.34 μM, 11.60 μM, 0.96 μM and 0.97 μM respectively, while compounds 2-5 were also found to be BChE inhibitors with IC50 1.25 μM, 3.93 μM, IC50 9.18μM and 10.20μM respectively. Compounds 2 (IC50 = 1.25±0.019uM) and 3 (IC50 = 3.93±0.36uM), showed potent BChE inhibitory potential than standard Galantamine (IC50 = 8.51±0.02uM). Besides this, compounds 2-9 were evaluated for glycation inhibition activity. Compound 5 (IC50 values 120.6+0.2uM) showed potent antiglycation potential than standard rutin (IC50=294.50+1.5uM). The size of the substituent, electron donating or withdrawing effect of substituents as well as the position of substituent on phenyl effects the activity.

Synthesis, Pharmacological Evaluation and In-Silico Studies of SomePiperidine Derivatives as Potent Analgesic Agents

In present study, some 4-piperidinopiperidine (PP) and 4-amino methylpiperidine (AMP) derivatives (PP1-3 and AMP4-9) have been synthesized to explore their analgesic potential. Activity of compounds evaluated by in-vivo thermal (tail immersion) method produced significant analgesia at different doses. Docking results explained good binding affinity of synthesized derivatives and potential interaction of all compounds with mu-opioid receptor. The pharmacophoric model of synthesized compounds showed possible structural features required for analgesic activity when compared with standards (Fentanyl, Morphine, Pethidine). Among all PP1, AMP5 and AMP6 emerged out as potent analgesic agents. Graphical abstract