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The present study envisioned some antioxidant candidates having 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole (TRY), 3-(2-bromoethyl)indole (BEI) and 7-azindole (AI) nucleus. Derivatives of these indole molecules were synthesized and their scavenging activity for reactive oxygen species (ROS) investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. T3, T42 exhibited significant radical scavenging potential which is comparable to ascorbic acid (standard), while T36 appeared as most potent antioxidant by displaying better scavenging activity than standard molecule. Molecular docking study revealed good binding score and interactions of T36 with target human antioxidant enzyme (PDB code: 3MNG) validating the results of biological activity.

In the current study a series of 4-(2-keto-1-benzimidazolinyl) piperidine have been newly synthesized and activities of 5-chloro-1-(4-piperidyl)-2-benzimidazolinone derivatives that is already reported have been tested and compared. Furthermore synthesized derivatives have been characterized by physical and spectral methods (HR-EIMS, HR-FABMS, 1H-NMR, 13C-NMR, UV, and FT-IR). All the derivatives were tested for leishmanicidal and anticancer activities. Results demonstrated that among all the derivatives compounds 4, 9, and 10 exhibited significant cytotoxic effects on HeLa cells and therefore tested at 10, 50 and 100 µM concentrations. Among all the eleven derivatives eight derivatives were found having leishmanicidal activity. Compounds 3, 4 and 10 exhibited significant activity with IC50 values in range of 7.06 ± 0.17 µg/mL − 84.6 ± 0.6 µg/mL. Furthermore, an attempt was made to develop a preliminary structure-activity relationship. Compound 4 found to be most active with IC50 = 7.06 ± 0.17 µg/mL against leishmaniasis. Compounds 4 and 10 possess both leishmanicidal and anticancer activities. From this study we identified a new class of compounds having potent leishmanicidal activity and anticancer activity.

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.

Background: Diabetes is co-morbid with various metabolic and psychological disorders. Diabetes and depression are both chronic conditions with allied adverse and complicated outcomes. Objectives: The current study was designed and planned accordingly to elucidate the associated frequency of depression with DM (Diabetes Mellitus) type 2 and prescribing practice of doctors depending on the distressing reality and threatening figures. Methodology: A prototype prospective study was monitored in different public and private sector hospitals and clinics of outpatient settings in Karachi after taking approval from the Ethical Review Board of Hamdard University. In this context, seven hundred patients having diabetes were covered in the study and their data were analyzed through the Statistical software version 20. Beck Depression Inventory (BDI) was the preferred approach to evaluate the depression level. Results: The outcome of the study established the fact of high prevalence for the co-morbidity of stress, anxiety and depression among patients with diabetes in Karachi, specifically among age bracket from forty to sixty years. Unfortunately, 80% (544) of diabetic patients in the study were suffering from depression and anxiety, while only 22.05% (120) patients were taking antidepressants and they were not counseled for the root cause of the disease. Severe depression (BDI score=38) was present in 100 subjects, moderate depression (BDI score=27) in 200 subjects, and mild depression was present in 175 of subjects. Being a patient of DM is itself a strong reason for contracting a depressive disorder. The result highlight improper treatment of depression in diabetic patients. Conclusion: However, the current situation demands to follow proper treatment through effective and appropriate drugs to treat the disease from progressing. Moreover, efforts should be undertaken to strengthen the healthcare system where practitioners, either doctors, pharmacists or nurses are liable for patient care in both the physical and psychological domains.

Diabetes mellitus is co-morbid with various metabolic and psychological disorders characterized by high blood glucose levels due to defects in insulin availability in body. Glucose work as a fuel to provide energy for all physical activities whereas in type 1 diabetes, the beta cells in the pancreas becomes unable to make insulin because of autoimmune disease, consequently there is no insulin to convert glucose leading to low energy level and other metabolic disorders. The disease is also called juvenile diabetes as usually starts to appear in childhood, that cannot be controlled but can be managed by timely diagnosis and care. The present study covers the case of a young child having type 1 diabetes in childhood and its consequences. The child inherited from paternal grandmother however other siblings were deficit. The case was become complicated because of poor timely investigations and management. Furthermore weak awareness and inappropriate healthcare practices made the disease more knotty. The work also covers the measures that should be taken by the health care providers through proper counseling and educating the parents and family, furthermore an accurate guidelines regarding nutrition, medications should be utmost. Self identification of having diabetes is necessary for school going children in order to manage abrupt hypoglycemic corollaries. Bangladesh Journal of Medical Science Vol.19(2) 2020 p.326-332

In the study of designing pharmacophore models for analgesic, a series of 4-[4–chloro-3- (trifluoromethyl)-phenyl]-4-piperidinol (TFMP) derivatives were synthesized and characterized by physical and spectral method (HR-EIMS, HR-FABMS, 1H-NMR, 13C-NMR, UV, and FT-IR). The analgesic action of the synthesized derivatives was estimated by means of Hot Plate Method. Most of the compounds displayed potent analgesic efficacy and an ultrashort to long duration of action. The results indicate that these compounds are useful as analgesics. Qualitatively nine compounds resemble morphine in pharmacological action, whereas three derivatives are devoid of any significant analgesic potential. In conclusion, among active compounds 3 (188%), 5 (137%), 6 (162%), and 8 (107%) respectively emerged as most effective analgesic and they depressed peripheral and centrally mediated pain by opioid dependent and independent systems.

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.

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

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

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 (IIV) 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.

The objective is to assess the awareness level and practice for the consumption of expired pharmaceuticals in general public of Karachi, Pakistan. In this regard, a cross-sectional study was conducted and completed from December 2013 to September 2014. Self-administered study instrument was used which consisted of total 11 variables regarding the assessment of participants’ perspective on product expiry and its usage was distributed to 120 participants. Data were analyzed in SPSS version16.0. Primarily descriptive nature was used while frequency percentages of respondents were computed for categorical variables. Mean ± SD were computed for assessment of knowledge scores. Overall response rate was 83.33% in which 74 male and 26 females filled the study instrument. Average scores of respondents’ awareness regarding expiry of pharmaceutical products was 4.62 ± 0.75. The qualification of respondents includes the graduates’ count (64.9% male and 65.4% females) while 16.2% male and 23.1% female were postgraduate. Response distribution of respondents showed that 93.2% male and 92.3% female were aware about the product expiry concept. Similarly, 87.8% male and 96.2% female were in favor for their non-utilization, as 89.2% male and 96.2% female reported its severe harmful effects. Overall, 87.8% male and 76.9% female were interested to discard such products. Interestingly, 82.4% male 73.1% female were in full opinion to check the product expiry date before its purchase whereas, 78.4% male and 92.3% female have their opinion to purchase long expiry products. Box plot regarding products preference and total aggregated knowledge scores showed consistency. Results concluded that the knowledge, responses and practices of participants were in favor for the non-utilization of expired pharmaceuticals.

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.

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

Cobalamins are the largest and structurally complex cofactors found in biological systems and have attracted considerable attention due to their participation in the metabolic reactions taking place in humans, animals, and microorganisms. Riboflavin (vitamin B2) is a micronutrient and is the precursor of coenzymes, FMN and FAD, required for a wide variety of cellular processes with a key role in energy-based metabolic reactions. As coenzymes of both vitamins are the part of enzyme systems, the possibility of their mutual interaction in the body cannot be overruled. A molecular docking study was conducted on riboflavin molecule with B12 coenzymes present in the enzymes glutamate mutase, diol dehydratase, and methionine synthase by using ArgusLab 4.0.1 software to understand the possible mode of interaction between these vitamins. The results from ArgusLab showed the best binding affinity of riboflavin with the enzyme glutamate mutase for which the calculated least binding energy has been found to be −7.13 kcal/mol. The results indicate a significant inhibitory effect of riboflavin on the catalysis of B12-dependent enzymes. This information can be utilized to design potent therapeutic drugs having structural similarity to that of riboflavin.

The HslVU is the proteasome-related two component system composed of HslV peptidase and HslU chaperone. It is involved in the degradation of an array of intracellular proteins. The presence of HslVU homologs in pathogenic microbes and its absence in human makes it an antimicrobial drug target. The functional HslVU complex forms when HslV dodecamer is flanked at both ends by HslU hexamers. In the HslVU complex, eight residues at the carboxy termini of HslU subunits intercalate into a clefts between two adjacent HslV subunits causing a conformational change in the active site of HslV which in turn results in the allosteric activation of HslV peptidase. Here, we report small molecules capable of activating HslV peptidase in the absence of its natural activator HslU ATPase. For this purpose, virtual screening of an in-house library of synthetic and natural compounds was performed to find out ligands mimicking the interaction of HslU carboxy terminus with HslV dodecamer. The benzimidazole, quinazoline and chromone derivatives were suggested by ligand docking to bind at the HslU carboxy termini intercalation pockets in the HslV dodecamer. This was confirmed by HslV activation and isothermal titration calorimetry assays with these compounds that gave ED 50 in sub-micromolar range (0.6–1.5 μM). The results showed for the first time that small, extracellular non-peptidic molecules can allosterically activate the peptide hydrolytic activity of HslV which in turn would initiate intracellular proteolysis.

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.

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.

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.

A variety of piperidines (2-12, 14-26) with variable substituents at N-atoms have been synthesized and evaluated as urease inhibitors. The synthesized compounds showed varying degree of urease inhibitory activity ranging from 31.97 to 254 microM. The size and electron-donating or -withdrawing effects of substituents influence the activity, which lead to the formation of urease inhibitors.

In this investigation, we report the presence of cholinomimetic and acetylcholinesterase (AChE) inhibitory constituents in betel nut, the most commonly used drug in the world after tobacco, ethanol and caffeine. The crude extract of betel nuts or Areca catechu (Ac.Cr) caused a dose-dependent (0.3-300 microg/mL) spasmogenic effect in the isolated rabbit jejunum. The spasmogenic effect was blocked by atropine, similar to that of acetylcholine (ACh), suggestive of muscarinic receptor mediated effect. Both the extract (0.3-10 microg/mL) and physostigmine (0.1-3.0 microM) potentiated the effect of a fixed dose of ACh (10 microM) in a dose-dependent fashion, suggesting acetylcholinesterase (AChE) inhibitory effect. This effect was confirmed in the in vitro assay where both the crude extract (1-100 microg/mL) and physostigmine inhibited the enzyme. In the in vivo model of gastrointestinal transit, Ac.Cr (10-30 mg/kg) enhanced the travel of charcoal meal and also exhibited a laxative effect in mice. The plant extract was subjected to activity-directed fractionation and all resultant fractions showed atropine-sensitive spasmogenicity in rabbit jejunum and also AChE inhibitory effect at doses similar to that for the parent crude extract, the ethyl acetate fraction being slightly less potent. Some of the known constituents of betel nut, including arecoline, were tested for the possible inhibitory effect on AChE, none were found active. The study provides first evidence for the presence of AChE inhibitory constituents in betel nut, though additional direct muscarinic stimulatory effect cannot be ruled out and this study provides sound scientific basis for some of the folkloric uses associated with betel nut chewing.

Syntheses of benzopyrones 1, 13, and their derivatives, as well as their phytotoxic (in vitro) and antifungal (in vitro) screening was carried out. Compounds 2, 7, 8, and 10 showed significant phytotoxic activity, whereas 3, 8, 10, and 12 exhibited significant antifungal (in vitro) activity.

In view of a role of pre- and postsynaptic serotonin (5-hydroxytryptamine; 5-HT) receptors in adaptation to stress, effects of 1-(1-naphthylpiperazine) (1-NP) were compared in unrestrained and repeatedly restrained adapted rats. In the first part of the study, effects of various doses (1.0-15 mg/kg ip) of 1-NP were monitored on brain 5-HT metabolism (presynaptic response) and on the activity (postsynaptic response) of rats in an activity cage to which the rats were habituated before the drug administration. The drug injected at doses of 2.5-15.0 mg/kg increased motor activity and decreased brain 5-hydroxyindoleacetic acid (5-HIAA) concentration in a dose-dependent manner. In the second part of the study, rats were restrained on wire grids 2 h/day for 5 days. First-day episode of 2-h restraint decreased 24-h cumulative food intake, water intake and growth rate. The decreases attenuated following second-, third- and fourth-day episodes of 2-h restraint were not observed following fifth-day episode of 2-h restraint stress, suggesting adaptation to the stress schedule has occurred. Serotonergic and motor responses to 1-NP in unrestrained and repeatedly restrained adapted rats were compared by injecting the drug at a dose of 5 mg/kg, a dose that above results suggested would not produce maximal effects on 5-HT metabolism or motor activity. Administration of 1-NP at a dose of 5 mg/kg increased motor activity and decreased brain 5-HIAA concentration in unrestrained and repeatedly restrained adapted rats. Increases of motor activity were much greater in repeatedly restrained adapted than unrestrained rats. Decreases of 5-HIAA concentration were comparable in the two groups. The results are discussed in the context of an increase in the effectiveness of postsynaptic 5-HT-1A and 5-HT-1B receptors and a decrease in the effectiveness of presynaptic 5-HT-1A (somatodendritic) and 5-HT-1B (terminal) receptors following adaptation to stress. It is suggested that these changes of receptor responsiveness might help coping with stress demand to produce adaptation to stress.

Alzheimer's disease (AD) has a progressive neurodegenerative pathology with severe economic and social impact. There is currently no cure, although cholinesterase inhibitors provide effective temporary relief of symptoms in some patients. Nowadays, drug research and development are based on the cholinergic hypothesis that supports the cognition improvement by regulation of the synthesis and release of acetylcholine in the brain. There are only five commercial medicines Donepezil, galantamine, memantine, rivastigmine, tacrine approved for treatment of AD. Natural products have played an important alternative role in the research for new acetylcholinesterase inhibitors, as exemplified through the discovery of galantamine. AD is the dementia associated with aging, which initially targets memory and progressively destroys the functions of the brain, as the neocortex suffers neuronal, synaptic, and dendritic losses. The whole phenomena proliferate due to deposition of amyloid plaques. The goal of the present work is to analyse the search on drugs for the treatment and prevention of AD in the light of Acetyl cholinesterase activity. It is based on systematisation of the data on biochemical and structural similarities in the interaction between physiologically active compounds and their biological targets related to the development of such pathologies.

Five new compounds have been isolated from the fresh fruits of Momordica charantia and their structures elucidated through spectroscopic studies. These include three pentacyclic triterpenes 13-hydroxy-28-methoxy-urs-11-en-3-one (momordicin), 13β,28-epoxy-urs-11-en-3-one (momordicinin), 24-[1′-hydroxy,1′-methyl-2′-pentenyloxyl]-ursan-3-one (momordicilin), a sterol 3β-hydroxy-stigmasta-5,14-dien-16-one (momordenol) and a monocyclic alcohol 1-hydroxy-1,2-dimethyl-2-[8′,10′-dihydroxy-4′,7′-dimethyl-11′-hydroxy methyl-trideca]-3-ethyl-cyclohex-5-en-4-one (momordol).

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.

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.

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.

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.

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.

Two series of variably N-substituted biperidines were synthesized by condensing various acid chlorides, alkyl halides and anhydrides with 1,4-bipiperidine. The new compounds were tested as tyrosinase inhibitors and a structure-activity relationship (SAR) study was carried out. Potent inhibition was observed in the case of the 4'-methylbenzyl substitution on this atom (IC50 = 1.72 microM) with this compound being a lead for future drug design. Additionally, calculations of the important QSAR molecular descriptors were done on the biperidine analogues after their 2 ps molecular dynamics (MD) simulations using molecular mechanics force field (MMFF) approaches. Using MD simulations potential and total energies were calculated for the energy minimized models of bipiperidine and the most active analogs 2, 3, 4, 6, 8 and 10.

The synthesis and selective biological screening of 7-hydroxy-4-methyl-2H-chromen-2-one (2), 7-hydroxy-4,5-dimethyl-2H-chromen-2-one (15) and some of their derivatives were carried out. Compound 13 was found to be most potent cytotoxic agent with LD50 = 126.69 microg/ml. In antibacterial assay the compounds showed a broad spectrum of activities. Compound 11 exhibited a very high degree of plant growth inhibition at three levels of concentration. Compound 4 showed very promising antifungal activity against Candida albicans. Compounds 12 and 13 demonstrated excellent antioxidant activity.

7-Hydroxy-4-methyl-2 H -chromen-2-one (2) , 7-hydroxy-4,5-dimethyl-2 H -chromen-2-one (15) and their some derivatives were synthesized for exploring selected biological screening. The compounds 9 and 13 had shown high degree of cytotoxic activity. Three compound 9 , 10 and 13 showed high degree of bactericidal activity amongst the present series.