New series of hydrazinyl thiazole derivatives of piperidin-4-one: Synthesis, structural elucidation, analgesic activity and comparative structure activity relationship.

Seven new hydrazinyl thiazole derivatives of piperidin-4-one (PE3-PE9) have been synthesized by cyclization of intermediate thiosemicarbazone derivative (PE2). Parent molecule (PE1) was synthesized by one pot total synthesis using Mannich condensation reaction. Percent yield of most of the compounds found in between 70-85%. Compounds were identified by spectroscopic analysis. In vivo analgesic activity was examined using tail flick method. One-way ANOVA was used to compare the mean latency time of synthesized derivatives with control and standard. Analgesic activity was discussed in terms of structural differences between compounds. Among allthe derivatives thiosemicarbazone derivative showed good analgesic activity (195.24%). Methoxy (-OCH3) and bromo (-Br) containing thiazole derivative also showed good pain reducing property (167.62%, 203%) at a dose of 30mg/kg.

Self-Medication in the COVID-19 Pandemic: Survival of the Fittest.

OBJECTIVE: After the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic, intense efforts to combat the novel coronavirus were undertaken, with many fatalities in most regions of the world. The high fatality rate and socioeconomic collapse affected the health of uninfected individuals because healthcare measures and scheduled clinical and hospital visits were avoided by people in an attempt to reduce their exposure to the contagion. The general population began self-medication practices as means to safeguard against exposure to the virus. METHODS: The present study investigated the effectiveness of self-medication compliance among the general population. For this purpose, a questionnaire on the Zenodo scale was developed and adults and teen respondents were asked to complete it, after providing consent. The data gathered were analyzed using IBM SPSS Statistics Version 26. RESULTS: The study amazingly found high compliance with self-medication among the focused population during the period of COVID-19. Estimated results showed a highly significant correlation of 0.000, P < 0.05, between the adaptation of self-medication and pandemic situation, which was estimated from chi-squared and Fisher test results. CONCLUSIONS: However, the fear of coronavirus made the practice, or malpractice, a survival of the fittest, innate ability of human nature.

Synthesis, characterization and analgesic studies of novel thiazole derivatives of 4-piperidone.

In this present study seven novel thiazole derivatives (PM3-PM9) were synthesized by cyclization of key intermediate thiosemicarbazone (PM2), derived from 4-piperidone (PM1). The parent 4-piperidone was synthesized by Mannich condensation reaction with good yield (89%). All the derivatives were characterized by UV, IR, 1HNMR and mass spectral analysis. All the synthesized products were screened for their in vivo analgesic activities. Most of the tested compounds exhibited potential to reduce pain and some of them showed good analgesic properties. Thiosemicarbazone derivative showed most significant activity (p-value 0.01). All the thiazole derivatives exhibited dose dependent mild to good analgesic activities. Among thiazole derivatives, chloro and nitro substituted compounds (PM3, PM4, and PM5) showed highest analgesic activities.

Potential nutraceutical benefits of basmati rice bran oil as analgesic, anti-inflammatory and anti-arthritis.

Numerous nutraceutical applications have been explored during the last decades. The present study is based on extraction of oil from super kernel basmati rice which has shown effective analgesic, anti- inflammatory, and anti-arthiritic activities. The feeding experiments on male Wister rats and female Sprague-dawley (SD) rats have elaborated the therapeutic value of variety of bioactive components including γ-oryzanol present in the oil.

Synthesis, Characterization and evaluation of antioxidant potential of 2, 6-diphenylpiperidine-4-one compounds and their novel imine derivatives.

In search of potent molecules having antioxidant activity the present work was designed to synthesize 2, 6-diphenylpiperidine-4-one compounds (1a and 1b) and their imine derivatives (2a, 2b, 3a, and 3b). Compounds 1a and 1b were synthesized by Mannich condensation reaction. The method was found to be simple, convenient with high yield and products were easily separated. Compounds 1a and 1b serves as an intermediate for the preparation of highly functionalized novel imine derivatives. Oxime (2a, 2b) and carbothioamide (3a, 3b) derivatives of 1a and 1b compounds were produced by condensation reaction with hydroxyl amine hydrochloride and thiosemicarbazide respectively. These compounds were characterized by IR, EI-mass and 1HNMR spectroscopy. The antioxidant activity of compounds was analyzed by 1, 1- dipheny1-2-picrylhydrazyl (DPPH) assay method. It was found that substituted aryl derivatives containing phenol and methoxy groups (1b, 2b and 3b) showed better antioxidant activity (IC50 values rang from 1.84-4.53µg/ml) than unsubstituted aryl derivative (1a, 2a and 3a) (IC50 rang from 6.46-11.13µg/ml). Compound 1b exhibited excellent antioxidant activity (IC50 1.84±0.15µg/ml) comparable to standard ascorbic acid (IC501.65± 0.16µg/ml).

Some novel piperidine analogues having strong alpha glucosidase inhibition.

The idea of this study is based on the marvelous fact of nojirimycin and deoxy nojirimycin, naturally occurring from piperidine class and having their role as alpha glucosidase inhibitors. In the present work some hydroxyl piperidine analogues have been synthesized and analysed for their hypoglycemic effect through glucosidase inhibition owing to the structural resemblance with nojirimycin. The activity was done by spectral absorbance analysis using acarbose as standard. Two analogues (I & IV) were found to pose excellent activity having 87.4 and 54.7% inhibition respectively, hence strengthening the idea of studying piperidine analogiues as glucosidase inhibitors due to structural similarity with nojirimycin.

Analgesic activity of alkyl piperidine derivatives.

Piperidine is the most significant scaffold which reveals therapeutic potential because of its conformationally flexible nature. During the course of present investigations synthetic quaternary salts of alkyl piperidine with various phenacyl bromides were explored for their possible analgesic activity. Compounds I analogs (1a-1f) and compound II analogs (IIa-IIf) showed varying degree of analgesic activity when compared with pethidine as standard and its duration by tail immersion method.

Synthesis and cytotoxic activity of some derivatives of alkyl piperidine.

Synthesis of novel phenacyl derivatives of alkyl piperidine as cytotoxic agents via simple and single step reaction procedure is going to be reported here. Twelve new compounds were successfully synthesized in moderate yield and in solid form. Their synthesis was confirmed by TLC, melting point, CHN analysis and through different spectral studies such as UV, IR, Mass and proton NMR. The advantages of this synthetic route are simple operation, mild reaction conditions and good yields. These newly synthesized derivatives were extensively explored for their cytotoxicity by brine shrimp lethality assay.

New benzimidazole derivatives as antiplasmodial agents and plasmepsin inhibitors: synthesis and analysis of structure-activity relationships.

The newly synthesized benzimidazole compounds were suggested to be inhibitors of Plasmodium falciparum plasmepsin II and human cathepsin D by virtual screening of an internal library of synthetic compounds. This was confirmed by enzyme inhibition studies that gave IC(50) values in the low micromolar range (2-48µM). Ligand docking studies with plasmepsin II predicted binding of benzimidazole compounds at the center of the extended substrate-binding cleft. According to the plausible mode of binding, the pyridine ring of benzimidazole compounds interacted with S1' subsite residues whereas the acetophenone moiety was in contact with S1-S3 subsites of plasmepsin II active center. The benzimidazole derivatives were evaluated for capacity to inhibit the growth of intraerythrocytic P. falciparum in culture. Four benzimidazole compounds inhibited parasite growth at ⩽3µM. The most active compound 10, 1-(4-phenylphenyl)-2[2-(pyridinyl-2-yl)-1,3-benzdiazol-1-yl]ethanone showed an IC(50) of 160nM. The substitution of a phenyl group and a chlorine atom at the para position of the acetophenone moiety were shown to be crucial for antiplasmodial activity.

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.

Biopharmaceutical evaluation of oral tablet Atenolol (100 and 50 mg) on local population.

An open-label, randomized study was designed to determine the bioavailability (BA); pharmacokinetic (PK) and pharmacodynamic (PD) behaviour of Atenolol 50 mg (two pills) and 100 mg (one pill) tablet manufactured by a national pharmaceutical industry. Peak plasma concentration (Cmax): 1.33 +/- 0.31 microg/ml, time to peak plasma concentration (Tmax): 2.2 +/- 0.27 hours, AUC (area under the plasma concentration-time curve) 6.34 +/- 2.1 microg-hr/ml for 100 mg tab and Cmax: 1.07 +/- 0.23 microg/ml, Tmax: 2.5 +/- 0.35 hours, AUC 4.97 +/- 1.09 microg-hr/ml for 50 mg (two pills) tab were observed. The BA and PK parameters such as Cmax, Tmax, are comparable to previous studies, although significant decrease in diastolic and systolic blood pressure (mmHg) upto a certain limit for a considerable duration was observed. However, relation between PK and PD may not be established due to regulatory biochemical feedback mechanism.

Effects of tryptophan and valine administration on behavioral pharmacology of haloperidol.

Development of antipsychotics with slight/no extra-pyramidal symptoms (EPS) and/or other side effects is one of the exploring fields of drug research. Haloperidol is a high potency typical neuroleptic used in the treatment of schizophrenia but produces muscles related side effects commonly known as EPS. These effects are not produced following the administration of atypical neuroleptics such as clozapine. A severe side effect of clozapine treatment is however, agranulocytosis. This involves investigation on the mechanism by which a typical neuroleptic acting via serotonergic mechanism tends to produce less or no EPS. The present study was, therefore, designed to determine the effect of serotonin precursor tryptophan and a large neutral amino acid other than tryptophan (valine) on the modulation of haloperidol induced catalepsy and akinesia. Cataleptic effects of the drug and activity reducing effects were monitored on inclined surface and in an activity box or open field respectively. The results are discussed in the context of a role of tryptophan and valine induced changes of brain serotonin in modifying the extrapyramidal and monoaminergic effects of the typical neuroleptic haloperidol. In the present study administration of TRP and valine decreased activity in rats, haloperidol-induced catalepsy' was not modulated by prior administration of tryptophan or valine. Brain serotonin levels were elevated by haloperidol treatment and correlated very well with the behavioral response. These findings suggest a possible serotonergic involvement in neuroleptic induced tardive dyskinesia and an amelioration of the disorder through TRP supplementation.

Neurochemical estimations of some new quaternary phenacyl-bromopiperidinium compounds.

Considering the fact that N-alkyl substituted quaternary ammonium salts of piperidinium bromide induce brain catecholamine and indoleamine metabolism (Black et al., 1986), we thought it may be valuable to investigate the effects of three selected phenacyl derivatives (I, V and VIII) of piperidine on brain monoamines metabolism in mice (100mg/kg body weight) assuming that these derivatives might alter the brain indoleamine and catecholamine levels differently. Studies are carried out by using HPLC technique. It was found that compound VIII possessed greater neuroleptic activity as compared to compounds I and V.

Pharmacokinetic differences of some generic tablet gliclazide 80 mg on Pakistani population.

The goal of rational drug therapy is to produce a desired pharmacological response in an acceptable and predictable manner while minimizing the occurrence of undesired events. The Pharmacokinetics of different generics of tablet gliclazide 80 mg was investigated on healthy (10 x 2), Pakistani subjects. For this exploration an open-label, randomized, two-period crossover (Balanced in Complete Block Design) study, was conducted The out come of the said study suggests that all generics were found analogous regarding pharmacokinetic behavior in-spite of having different excipients, concentration of excipients, sources of raw material, manufacturing process, machinery, resources and also inter individual variation of the study. Results of the study also undoubtedly advocate that generics manufactured in different manufacturing units of Pakistan are near to the standard formulation and produce comparable results. No significant differences in pharmacokinetics parameters were observed, however, minor differences might narrate with inter individual variation in human volunteers and in different generic as well as different pharmaceutical unit.