Molecular docking, synthesis and biological evaluation of phenacyl derivatives of 9-aminoacridine as anti-Alzheimer's agent.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder mainly characterized by progressive deterioration of memory and impaired cognitive function. The most promising approach for symptomatic relief of AD is to inhibit acetylcholinesterase (AChE). On the basis of this approach in-house library of 9-aminoacridine derivatives were constructed and allowed to docked against human acetylcholinesterase (hAChE) (PDB ID: 4EY7), using MOE 2018.01 and PyRx 0.9.2 (AutoDock Vina). Top ranked and best fitted molecules were synthesized by targeting the 9-amino group of aminoacridine with substituted phenacyl halides. Anti-Alzheimer's potential was checked by in vitro AChE inhibition, antioxidant activity (DPPH scavenging ability) and fibril disaggregation. Subjected ligands suggested as promising multitargeted candidate with pronounced results in term of IC50 values (AChE inhibition 2.400-26.138µM), however, none of them showed potential towards fibril inhibition.

Synthesis of some novel analogues of 4-(1-Pyrrolidinyl) Piperidine and their effect on plasma glucose level.

In the present study some compounds of 4-(1-Pyrrolidinyl) Piperidine (I) have been synthesized. Structures of compounds were confirmed by using HNMR, IR, Mass and UV spectrophotometer techniques. All the derivatives (II, III, IV and V) and the parent compound (I) at the dose of 100 mg/kg were evaluated for their effect on plasma glucose level. Compound (II) was the only derivative which showed effect on plasma glucose level.

Synthesis and pharmacological activities of 7-azaindole derivatives.

As a part of our program to discover novel analogues of 7-azaindole (1H-Pyrrolo[2,3-b] pyridine) having useful biological activities, some derivatives have been synthesized and evaluated for their analgesic and hypotensive activity. Compounds evaluated by thermal stimuli (tail immersion method) at the dose of 50 mg/kg of body weight revealed significant analgesic activity. Pethidine was used as reference drug. Same compounds tested at the dose of 75 mg/kg of body weight showed toxicity. Compounds tested for their effect on blood pressure in normotensive rat produced slight fall in blood pressure.

Pharmacological activity of morpholino compound.

The pharmacological effect of morpholino compound in different biological field is of great importance for researchers and investigators. They are working day and night to synthesize pharmacologically more effective morpholino derivatives with less toxic effects. This kind of pharmacological screening of synthesized compounds can lead to the discovery of biologically useful compounds. The findings of the present study are encouraging, since present compound showed a promising analgesic activities and anti-inflammatory. Chemically synthesized morpholino compound are tested for its analgesic and inflammatory activities in intact albino mice ad rat. Compound was administered orally in different doses using the tail immersion test in mice for analgesic activity. The results of this study demonstrated that compound has inhibitory effect on arachidonic acid metabolisms via cyclooxygenase pathway or we can say the inhibition of prostaglandins biosynthesis. Classical non-steroidal anti-inflammatory drug, which inhibits cyclooxygenase, can shift arachidonic metabolism to lipoxygenase products. These findings reflect a new fact of pharmacological action of this compound like inhibition of arachidonic acid pathway in vivo. It can be concluded that the present study revealed a fair success rate but it is necessary to carry out further investigation to confirm the results.

Antibacterial activity of 1-methyl-7-methoxy-beta-carboline and its phenacyl and coumarine analogues.

Antibacterial activity of 1-methyl-7-methoxy-beta-carboline (harmaline) and its phenacyl and coumarine analogues 1-(3-nitro-phenyl)-(2-(7-methoxy-1-methyl-1,3,4,9-tetrahydro-beta-carbolin-2-yl)-ethanone (II), 1-(3,4-dihydroxy-phenyl)-2-(7-methoxy-1-methyl-1,3,4,9-tetrahydro-beta-carbolin-2-yl)-ethanone (III) 7-(methoxy-beta-carboline),15-24,de-hydro(19,20-dimethoxy)coumarine (IV), 7-(methoxy-beta-carboline)15-24,dehydro(20-methoxy)coumarine (V) were studied by disc diffusion method. All compounds were tested against three gram positive and four gram-negative bacteria. Parent compound showed good activity. All compounds revealed better results against gram positive as compared to gram-negative bacteria. 1-(3,4-Dihydroxy-phenyl)-2-(7-methoxy-1-methyl-1,3,4,9-tetrahydro-beta-carbolin-2-yl)-ethanone (III) was found most potent compound showing broad spectrum activity when compared with all synthesized analogues. Coumarine analogues showed more or less same activity indicating that number and position of methoxy groups are not important regarding antimicrobial activity.

Synthesis of 4-hydroxypiperidine derivatives and their screening for analgesic activity.

Six substituted phenacyl derivatives of 4-hydroxypiperidine were prepared and their structures were confirmed through spectroscopic techniques. These newly synthesized derivatives were also screened for analgesic activity by chemical and thermal methods. Only halogenated phenacyl derivatives demonstrated more or less protection against acetic acid induced writhing in mice where as rest of three derivatives were found inactive when screened by this chemical method. Similarly all the six derivatives were proved inactive by tail flick test.

Studies on the effects of piperidine derivatives on blood pressure and smooth muscles contractions.

Ten substituted phenacyl derivatives of 4-hydroxypiperidine were synthesized and studied for their effects on the mean arterial blood pressure (MABP) in normotensive anaesthetized rats and smooth muscles contractions of isolated rabbit jejunum. Two derivatives caused fall in blood pressure at the dose of 10-20 mg/kg and one rise in blood pressure at the dose of 20 mg/kg. Two compounds exhibited biphasic response (hypotensive followed by hypertensive) and one gave triphasic response at 10 mg/kg dose. Rest of four derivatives were found devoid of any effect on mean arterial blood pressure up to the dose of 30 mg/kg. All the derivatives except two caused relaxant effect on the spontaneous contraction of rabbit jejunum at the dose range of 0.1-2 mg/kg.

Effect of environments on human functions: studies on water metabolism.

The purpose of this review is to study general behaviour of human systems with respect to the environmental conditions. This type of work will be of profound significance to record the effect of medical treatment in various climatic zones of the world (Arayne and Saify, 1975). We attempted to discuss various facts which would be helpful for tackling the health problems of the people residing in these areas. The statistical data is avoided at the moment and a descriptive pattern is adapted in order to express views, about one of the important aspects of medical science.

Synthesis and anti-microbial screening of some piperidine derivatives.

Synthesis of piperidine derivatives viz, 1-(4'-methoxy phenacyl)-N-methyl piperidinium bromide, and 1-(4'-nitrophenacyl)-N-methyl piperidinium bromide, and 1-(3', 4'-dihydroxy phenacyl)-N-methyl piperidinium chloride was carried out by quarternizing N-methyl piperidine with corresponding phenacyl halides. The structures of these compounds were elucidated by spectroscopic techniques such as UV, IR, EI mass and 1H-NMR. The compounds were subjected to antimicrobial screening in quantities of 10 mg/ml dissolved in DMSO. Disc diffusion method was used to observe the significance of these compounds against seven bacterial and one fungal cultures.

Cineole as skin penetration enhancer.

Cineole is a chief constituent of eucalyptus oil and constitutes almost 80% of this essential oil. A study was conducted on skin penetration enhancing capacity of cineole (1, 8-cineole) towards the permeation of 5 flurouracil in excised rat skin; it caused almost 83 fold increase in drug permeability co-efficient, the mode of action of acceleration may be described by combined process of partition and diffusion.

Synthesis of some phenacyl nicotinates as potential anticholesterolemic agents.

Three anticholesterolemic agents, 2,4-dimethoxy phenacyl nicotinium bromide, 2,5-dimethoxy-phenacyl-nicotinium bromide, and 2,3,6-tribromo 3,5-dimethoxy-phenacyl-nicotinium bromide, were synthesized and their chemical structures were determined by spectroscopic method.

Neurochemical and extra pyramidal effects of atypical neuroleptic clozapine in rats.

In view of a possible role of serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) in neuroleptic-induced muscle rigidity and catalepsy, the present study is designed to investigate the neurochemical and extrapyramidal effects of atypical antipsychotic/neuroleptic drug i.e., Clozapine (CZP) on the metabolism of serotonin and dopamine particularly in the caudate (a region of the brain involved in the control of movement), accumbens and rest of the rat brain. Interaperitoneal (i.p) injections of CZP at doses of 5.0 & 10 mg/kg decreased significantly (p<0.01) locomotor activity in familiar (home cage) environment. CZP produced a significant (P<0.01) cataleptic response only at doses of 10 mg/kg used. Maximal cataleptic effects in rats occurred at high doses of CZP. Acute administration of CZP significantly (p<0.01) decreased levels of NA in accumbens at all the doses used. Significant increases (p<0.01) in the levels of NA observed in rest of the brain only at moderate dose (5 mg/kg) of CZP. Results showed significant (p<0.01) increases in the levels of caudate DA following the administration of CZP at 10 mg/kg. However administration of CZP at all the doses produced similar significant (p<0.01) increases in the levels of HVA in all the regions of the rat brain. Overall insignificant effects of CZP occurred on brain regional TRP. However, plasma TRP significantly (p<0.01) increased at 2.5 mg/kg dose of CZP. Administration of CZP at doses of 2.5 and 10 mg/kg significantly (p<0.01) decreased 5-HT levels in the rest of the brain. Administration of CZP produced insignificant (p>0.05) effects on 5-HIAA levels in the caudate and accumbens regions but CZP at doses of 2.5 and 5 mg/kg significantly (p<0.01) decreased 5-HIAA levels in the rest of the brain. Neurochemical and extrapyramidal effects of atypical antipsychotic (clozapine) are discussed in relation to a potential therapeutic profile in rats.

Assessment of Anemone pulsatilla for some biological activities.

Preliminary screening of herbal extracts employs the determination of their biological activity and the estimation of their therapeutic potential. This eliminates the unnecessary effort of fractionation and purification of constituents unimportant from the practice pharmacological point of view. It also gives a scientific basis to the herbs traditionally used in folk medicine. Thus, during the present investigation the spasmolytic effect of Anemone pulsatilla extract on isolated tissues of rabbit jejunum was evaluated. In addition the pharmacological screening of Anemone pulsatilla extract was also earned out.

Cardiac and intestinal contractions under the influence of triturated drug dilutions.

Triturated dilutions of acetylcholine and adrenaline are found to produce reverse effects than their parent one on the mechanical performance of mammalian heart and intestine in vitro. However, there is a variation in the magnitude of reverse response observed for both the tissues. It is concluded that variation in the effect of triturated dilutions is probably due to handling and shaking of the diluted drug before use in experiments. In addition, no relation exists between degree of dilution and the magnitude of response for both the tissues.

Role of quinone moiety as antitumour agents: a review.

Quinone antitumour agents with wide spectrum of activity have been extensively used in different forms of human cancers. Quinones have been isolated either from animals, microorganisms or plants. Extensive research on quinone compounds is going on to discover novel effective antitumour compound. We also discussed the mechanism of action, which have not been fully clarified. In this review we cover all the above-mentioned aspects to emphasize the importance of quinone moiety as antitumour agents.

Comparative studies on nicotinic acid derivatives as hypolipoproteinemic agents.

Nicotinic acid and its related compounds are well known lipid lowering agents but the use of nicotinic acid in clinical practice is limited because of its side effects. To reduce the unwanted effects, new derivatives of nicotinic acid have been synthesized and tested in control and pathological animals for their antilipoproteinemic effects. Two newly synthesized derivatives of nicotinic acid i.e. 3-methoxy phenacyl nicotinium bromide (T1) and 2-methoxy phenacyl nicotinium bromide (T2) have been screened for their hypolipoproteinemic effects in white male rabbits. The compounds were administered in the doses of 30 mg/day and the results were compared with aspirin taken as the reference drug. The present work revealed that both of these synthesize compounds exhibited marked effects on plasma lipoproteins assuming that these compounds exerted their action by inhibiting hepatic production of very low density lipoprotins (VLDL), ultimately leading to reduction in low density lipoprotein. Clofibrate and aspirin are taken as standards to evaluate the potentials of these agents for their effects on lipid.

Neurochemical effects of 8-hydroxy-2-di-n-propylamino tetralin in rats treated with haloperidol.

In view of a possible role of presynaptic serotonin (5-hydroxytryptamine, 5-HT) receptors in the precipitation of extrapyramidal side effects (EPS), the present study was designed to investigate the neurochemical effects of a selective 5-HT1A ligand, 8-hydroxy-2- (di-n-propylamino) tetralin (8-OH-DPAT) in rats following single (5 mg/kg) and repeated (two-times a day for 9 days at dosage of 5mg/kg) haloperidol administration. Haloperidol plus 8-OH-DPAT injected animals exhibited a decrease in dopamine (DA) and an increase in DA metabolite homovanillic acid (HVA) levels in the striatum and rest of the brain. The two groups of animals exhibited comparable levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the striatum and rest of the brain. Animals injected with haloperidol and killed 24 hrs after the last injection of haloperidol exhibited higher DA and HVA levels in the striatum but not in the rest of the brain. Conversely, dihydroxyphenylacetic acid (DOPAC), the other metabolite of DA, decreased in the rest of the brain. 5-HIAA concentrations increased in the striatum but not in the rest of the brain. Administration of 8-OH-DPAT significantly decreased 5-HT and 5-HIAA levels in the rest of brain and did not alter 5-HIAA in the striatum of repeated saline injected rats. Conversely, same dose of 8-OH-DPAT injected to repeatedly haloperidol injected animals did not decrease 5-HT and 5-HIAA concentrations in the rest of the brain but decreased 5-HIAA levels in the striatum. No effect of 8-OH-DPAT injections occurred on striatal or rest of the brain DA metabolism in repeatedly saline injected animals except that DOPAC decreased in the striatum of both groups. The results are discussed in the context of a role of somatodendritic 5-HT1A receptors in the regulation of DA metabolism following single and repeated administration of haloperidol. It is suggested that an increase in the responsiveness of these receptors may be involved in the precipitation of EPS observed in patients on haloperidol therapy.

A comparative study of omega-3-fatty acids obtained from marine fish and bezafibrate alone and in combination as hypolipidemic agents.

The fish oil and its constituents have been studied in detail with special reference to ailments. The discovery of omega-3 fatty acids led to a detailed investigation about its effect and role as anti-cholesterolemic agents. The effect of fish oil alone and in combination with acid derivatives was found to be a potent cholesterol and triglycerides lowering agent. Comparative studies of fish oils and bezafibrate led to the formulation of new therapeutic combination having lesser side effects and toxicity.

A study on fatty acid composition of fish oil from two marine fish, Eusphyra blochii and Carcharhinus bleekeri.

Two species of marine fish found in coastal waters of Karachi (Pakistan) were studied, Eusphyra blochii (Hammer-headed Shark) and Carcharhinus bleekeri (Shark) for their fatty acid composition. The isolation, identification and characterization of these fatty acids were carried out by gas liquid chromatography (GLC) and a combination of TLC-GLC technique. A large variation was observed between hammer-headed shark liver oil and shark liver oil. Twenty five individual fatty acids from the oil of marine fish were analyzed among those the palmitic acid was a major saturated fatty acid while stearic acid was the other major constituent. Among unsaturated fatty acids monoenoic e.g. oleic and palmitoleic acids were the major constituents and traces of dienoic and trienoic fatty acids were also found. In addition medicinally important polyunsaturated fatty, acid eicosapentaenoic and docosahexaenoic acids were also identified.

Antimicrobial activity of some commonly used herbs.

In the present study some herbal extracts have been tested for their antibacterial activity using seven different strains of Gram positive and Gram negative bacteria to measure the zone of inhibition. Extracts were found devoid of activity against all the microorganisms.