Displaying publications 1 - 20 of 81 in total

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  1. PALLISTER RA
    Med J Malaya, 1955 Mar;9(3):212-5.
    PMID: 14393211
    Matched MeSH terms: Piperazines/therapeutic use*
  2. Chen PC
    Med J Malaya, 1970 Mar;24(3):176-82.
    PMID: 4246796
    Matched MeSH terms: Piperazines/therapeutic use
  3. Usman A, Chantrapromma S, Fun HK, Poh BL, Karalai C
    Acta Crystallogr C, 2002 Mar;58(Pt 3):o136-8.
    PMID: 11870305
    In the title 1/2/2 adduct, C(4)H(12)N(2)(2+) x 2C(6)H(3)N(2)O(5)(-) x 2H(2)O, the dication lies on a crystallographic inversion centre and the asymmetric unit also has one anion and one water molecule in general positions. The 2,4-dinitrophenolate anions and the water molecules are linked by two O-H...O and two C-H...O hydrogen bonds to form molecular ribbons, which extend along the b direction. The piperazine dication acts as a donor for bifurcated N-H...O hydrogen bonds with the phenolate O atom and with the O atom of the o-nitro group. Six symmetry-related molecular ribbons are linked to a piperazine dication by N---H.O and C---H.O hydrogen bonds.
    Matched MeSH terms: Piperazines
  4. Salga SM, Ali HM, Abdullah MA, Abdelwahab SI, Wai LK, Buckle MJ, et al.
    Molecules, 2011 Nov 07;16(11):9316-30.
    PMID: 22064271 DOI: 10.3390/molecules16119316
    Some novel Schiff bases derived from 1-(2-ketoiminoethyl)piperazines were synthesized and characterized by mass spectroscopy, FTIR, UV-Visible, 1H and 13C-NMR. The compounds were tested for inhibitory activities on human acetylcholinesterase (hAChE), antioxidant activities, acute oral toxicity and further studied by molecular modeling techniques. The study identified the compound (DHP) to have the highest activity among the series in hAChE inhibition and DPPH assay while the compound LP revealed the highest activity in the FRAP assay. The hAChE inhibitory activity of DHP is comparable with that of propidium, a known AChE inhibitor. This high activity of DHP was checked by molecular modeling which showed that DHP could not be considered as a bivalent ligand due to its incapability to occupy the esteratic site (ES) region of the 3D crystal structure of hAChE. The antioxidant study unveiled varying results in 1,1-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. This indicates mechanistic variations of the compounds in the two assays. The potential therapeutic applications and safety of these compounds were suggested for use as human acetylcholinesterase inhibitors and antioxidants.
    Matched MeSH terms: Piperazines/chemistry*
  5. Yong CM, Yehgambaram PAP, Lee SWH
    PLoS One, 2024;19(2):e0298130.
    PMID: 38300930 DOI: 10.1371/journal.pone.0298130
    INTRODUCTION: Ovarian cancer is one of the most common cancer among women in Malaysia. Patients with ovarian cancer are often diagnosed at an advanced stage. Despite initial response to surgery and chemotherapy, most patients will experience a relapse. Olaparib has been reported have promising effects among BRCA mutated ovarian cancer patients. This study aimed to evaluate the cost-effectiveness of olaparib as a maintenance therapy for BRCA ovarian cancer in Malaysia.

    METHODS: We developed a four-state partitioned survival model which compared treatment with olaparib versus routine surveillance (RS) from a Malaysian healthcare perspective. Mature overall survival (OS) data from the SOLO-1 study were used and extrapolated using parametric models. Medication costs and healthcare resource usage costs were derived from local inputs and publications. Deterministic and probabilistic sensitivity analyses (PSA) were performed to explore uncertainties.

    RESULTS: In Malaysia, treating patients with olaparib was found to be more costly compared to RS, with an incremental cost of RM149,858 (USD 33,213). Patients treated with olaparib increased life years by 3.05 years and increased quality adjusted life years (QALY) by 2.76 (9.45 years vs 6.40 years; 7.62 vs 4.86 QALY). This translated to an incremental cost-effectiveness ratio (ICER) of RM 49,159 (USD10,895) per life year gained and RM54,357 (USD 12,047) per QALY gained, respectively. ICERs were most sensitive to time horizon of treatment, discount rate for outcomes, cost of treatment and health state costs, but was above the RM53,770/QALY threshold.

    CONCLUSION: The use of olaparib is currently not a cost-effective strategy compared to routine surveillance based upon the current price in Malaysia for people with ovarian cancer with BRCA mutation, despite the improvement in overall survival.

    Matched MeSH terms: Piperazines*
  6. Kow CS, Ramachandram DS, Hasan SS
    Angiogenesis, 2023 Nov;26(4):481-483.
    PMID: 37530975 DOI: 10.1007/s10456-023-09889-2
    Imatinib, an ABL tyrosine-kinase inhibitor, shows promise in restoring endothelial barrier function in patients with COVID-19, thus, preventing cytokine leakage from the alveolar compartment to the systemic compartment. COVID-19 is characterized by an alveolar cytokine storm, and imatinib has been shown to strengthen the endothelial barrier and mitigate alveolar inflammatory responses by modulating NF-κB signaling. Incorporating imatinib into COVID-19 treatment strategies offers a novel approach to safeguard the endothelial barrier and address the complex pathophysiology of the disease, including its potential implications in long COVID. Given that endothelial dysfunction plays a central role in COVID-19 progression and long COVID development, protecting the endothelial barrier during acute infection is crucial in preventing the persistent endothelial dysfunction associated with long COVID.
    Matched MeSH terms: Piperazines/pharmacology
  7. Rosnah Shamsudin, Wan Ramli Wan Daud, Mohd Sobri Takrif, Osman Hassan
    MyJurnal
    The physico-mechanical properties data of fruits are important in the design of various handling, packing, and storage and transportation system. The physical-mechanical properties of pineapple fruit from the Josapine variety, namely the weight of the fruit (with and without peel), pulp to peel ratio, diameter of the whole fruit (with and without peel), at three different positions along the longitudinal axis of the fruit, length of the fruit (with and without peel) and the length of crown were studied using the standard method at seven stages of maturity during storage at 25°C and 52% (RH). The effect of fruit maturity on the firmness of each fruit at three different locations was measured using a cylindrical die of 6 mm in diameter with the Instron Universal Testing Machine. The results indicated that the average total weight of a single fruit is 886.86 ± 49.67 g. The average pulp to peel ratio is 1.91. The average diameter (with and without peel) was 86.83 ± 5.24 mm and 80.95 ± 4.15 mm (top section), 100.77 ± 3.84 mm and 90.19 ± 3.73 mm (middle section) and 97.17 ± 3.49 mm and 73.30 ± 5.11 mm (bottom section), respectively. The average length of the fruit (with and without peel) was 126.65 mm and 113.64 mm, respectively. The average length of crown was 89.13 mm. The firmness of the fruits was found to decrease with the stage of maturity. These data are important in determining the optimum stage of maturity for fruit processing.
    Matched MeSH terms: Piperazines
  8. Zin NM, Baba MS, Zainal-Abidin AH, Latip J, Mazlan NW, Edrada-Ebel R
    Drug Des Devel Ther, 2017;11:351-363.
    PMID: 28223778 DOI: 10.2147/DDDT.S121283
    Endophytic Streptomyces strains are potential sources for novel bioactive molecules. In this study, the diketopiperazine gancidin W (GW) was isolated from the endophytic actinobacterial genus Streptomyces, SUK10, obtained from the bark of Shorea ovalis tree, and it was tested in vivo against Plasmodium berghei PZZ1/100. GW exhibited an inhibition rate of nearly 80% at 6.25 and 3.125 μg kg-1 body weight on day four using the 4-day suppression test method on male ICR strain mice. Comparing GW at both concentrations with quinine hydrochloride and normal saline as positive and negative controls, respectively, 50% of the mice treated with 3.125 μg kg-1 body weight managed to survive for more than 11 months after infection, which almost reached the life span of normal mice. Biochemical tests of selected enzymes and proteins in blood samples of mice treated with GW were also within normal levels; in addition, no abnormalities or injuries were found on internal vital organs. These findings indicated that this isolated bioactive compound from Streptomyces SUK10 exhibits very low toxicity and is a good candidate for potential use as an antimalarial agent in an animal model.
    Matched MeSH terms: Piperazines/isolation & purification; Piperazines/pharmacology*; Piperazines/chemistry
  9. Liang Q, Zhang S, Liu J, Zhou X, Syamimi Ariffin N, Wei J, et al.
    Bioorg Chem, 2024 Sep;150:107596.
    PMID: 38941699 DOI: 10.1016/j.bioorg.2024.107596
    A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX. Moreover, compound 9o exhibited superior antitumor activities against breast cancer cells under hypoxia than that of normoxia conditions. Mechanism studies revealed that compound 9o could act as DNA intercalator and effectively suppressed cell migration, arrested the cell cycle at G1/S phase and induced apoptosis in MDA-MB-231 cells, while inducing ferroptosis accompanied by the dissipation of MMP and the elevation intracellular levels of ROS. Notably, in vivo studies demonstrated that 9o effectively inhibited tumor growth and metastasis in a highly metastatic murine breast cancer 4 T1 xenograft model. Taken together, this study suggests that compound 9o represents a potent and selective CA IX inhibitor and ferroptosis inducer for the treatment of TNBC.
    Matched MeSH terms: Piperazines/chemical synthesis; Piperazines/pharmacology; Piperazines/chemistry
  10. Normala I, Hamidin A
    Med J Malaysia, 2009 Sep;64(3):240-1.
    PMID: 20527278 MyJurnal
    The use of atypical antipsychotic agents in early onset schizophrenia is rising despite its limited data on efficacy, safety and tolerability. Early onset schizophrenia warrants effective pharmacological treatment that is safe and well tolerated by children and adolescent population. Existing atypical agents are not completely free of side effects. Aripiprazole has unique properties that differ from other atypical antipsychotics and fill up the missing gaps, as it is associated with minimal metabolic complications and extrapyramidal side effects that are more commonly seen in other atypical agents. It offers a better option for this population and may possibly be considered as first line treatment in future. This case report demonstrates the efficacy and safety of Aripiprazole in children and adolescent population.
    Matched MeSH terms: Piperazines/adverse effects; Piperazines/therapeutic use*
  11. Tan HM, Moh CL, Mendoza JB, Gana T, Albano GJ, de la Cruz R, et al.
    Urology, 2000 Oct 1;56(4):635-40.
    PMID: 11018621 DOI: 10.1016/s0090-4295(00)00688-9
    OBJECTIVES:
    To evaluate the efficacy, safety, and tolerability of oral sildenafil in Asian men with erectile dysfunction of various causes (organic, psychogenic, or mixed) and of more than 6 months' duration.

    METHODS:
    In this double-blind, parallel-group trial conducted at eight centers in Malaysia, the Philippines, and Singapore, 254 men, 26 to 78 years old, were randomized to 12 weeks of sildenafil or placebo taken as needed 1 hour before anticipated sexual activity. Initially, the sildenafil (n = 127) or matching placebo (n = 127) dose was 50 mg but could be increased to 100 mg or decreased to 25 mg because of a lack of efficacy or intolerance, respectively. Efficacy was assessed by the 15-question International Index of Erectile Function, patients' event logs of sexual activity, and a global efficacy question about erections.

    RESULTS:
    The two primary efficacy variables relating to achievement and maintenance of an erection sufficient for sexual intercourse, as assessed by the mean scores for International Index of Erectile Function question 3 (4.22 versus 2.59) and question 4 (4.15 versus 2.41), were both significantly higher with sildenafil than with placebo (P <0.0001). In addition, the five separate International Index of Erectile Function domains of sexual function, the percentage of successful intercourse attempts, and the global efficacy assessment of erections revealed significantly greater treatment effects in favor of sildenafil (P <0.0001 versus placebo for all variables). Treatment-related adverse events occurred in 22.8% of patients who received sildenafil and in 10.2% of those who received placebo.

    CONCLUSIONS:
    Sildenafil is an effective and well-tolerated treatment for Asian men with erectile dysfunction of broad-spectrum etiology.
    Matched MeSH terms: Piperazines/adverse effects; Piperazines/therapeutic use*
  12. Lim PH, Ng FC, Cheng CW, Wong MY, Chee CT, Moorthy P, et al.
    J Int Med Res, 2002 Mar-Apr;30(2):137-43.
    PMID: 12025521 DOI: 10.1177/147323000203000206
    Safety and tolerability of sildenafil citrate was assessed in a population subset of 60 Singaporean men with erectile dysfunction taken from the Asian Sildenafil Efficacy and Safety Study (ASSESS-I), a double-blind, placebo-controlled, flexible-dose study. The men, from two centres, with > or = 6 months' history of erectile dysfunction, were randomized to two treatment arms for 12 weeks. One group (30 patients) received sildenafil (initial dose 50 mg taken 1 h before sexual activity for the first 2 weeks, increased to 100 mg or decreased to 25 mg, according to efficacy and/or tolerability). The remaining 30 patients received a matching placebo. Incidence and type of adverse effects were evaluated at 2, 4, 8 and 12 weeks. Nine patients (30.0%) on sildenafil (33.1% in the full ASSESS-I study) and one patient (3.3%) on placebo (22.8% in the full ASSESS-I study) experienced treatment-related adverse events, the most frequent being headache in the sildenafil group (reported by five patients [16.7%]; 11.0% in the full ASSESS-I study). Flushing, visual disturbance, dizziness, insomnia, myalgia and back pain each occurred in one patient in the sildenafil group (3.3%); in the placebo group, one patient (3.3%) had headache. Importantly, the incidence of cardiovascular and respiratory system adverse events were relatively less than in the full ASSESS-I population (cardiovascular 3.3% in the present study versus 10.2% in the full ASSESS-I population; respiratory 3.3% versus 5.5%). All adverse events were transient and mild, and did not lead to treatment withdrawal. There was no effect on sitting blood pressure, heart rate or standard laboratory parameters; more importantly, there was no incidence of myocardial infarction, stroke or priapism. These results should reassure Singaporean patients and their physicians of the safety of sildenafil for erectile dysfunction.
    Matched MeSH terms: Piperazines/adverse effects*; Piperazines/therapeutic use
  13. Gao Q, Zhu J, Zhao W, Huang Y, An R, Zheng H, et al.
    Clin Cancer Res, 2022 Jun 01;28(11):2278-2285.
    PMID: 35131903 DOI: 10.1158/1078-0432.CCR-21-3023
    PURPOSE: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer.

    PATIENTS AND METHODS: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453).

    RESULTS: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs.

    CONCLUSIONS: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201.

    Matched MeSH terms: Piperazines/administration & dosage; Piperazines/adverse effects
  14. Man CN, Noor NM, Lajis R
    J Chromatogr A, 2011 Sep 28;1218(39):7055-60.
    PMID: 21872876 DOI: 10.1016/j.chroma.2011.08.037
    Sildenafil analogues have been found adulterated in herbal preparations and food products that claim to have natural aphrodisiacs. In this study, a gas chromatography-mass spectrometry (GC-MS) assay was developed for the screening and identification of thioketone analogues of sildenafil. Thiopyrazolopyrimidine, a precursor or a cleavage product of thioketone analogue, exhibited characteristic fragment ions of m/z 328 and m/z 299 was found to be the best marker to screen the presence of general thioketone analogues. Identification by GC-MS assay was rapid and specific as all the studied thioketones showed characteristic mass fragmentations including their intact molecular ions. The developed GC-MS assay had successfully identified thiosildenafil, thiohomosildenafil and thiodimethylsildenafil in herbal preparation and food products.
    Matched MeSH terms: Piperazines/isolation & purification; Piperazines/chemistry*
  15. Teoh M, Narayanan P, Moo KS, Radhakrisman S, Pillappan R, Bukhari NI, et al.
    Pak J Pharm Sci, 2010 Jan;23(1):35-41.
    PMID: 20067864
    Imatinib inhibits Bcr-Abl, c-KIT and PDGFR kinases. It is approved for the treatment of chronic myeloid leukemia (CML), gastrointestinal stromal tumors (GIST) and has further therapeutic potential. Male ICR mice were given imatinib PO (50 or 25 mg/kg, 5 doses every 2 h); euthanized 2 h after the last dose administration; plasma, liver, brain, spleen and kidney were collected and imatinib concentration measured by an optimized HPLC method for quantification in tissues. Methanol (1:1 v/v plasma) and pH 4, 40:30:30 (v/v/v) water-methanol-acetonitrile at 5 ml/g (brain) and 10 ml/g (spleen, kidney, liver) ratio was added to the samples, homogenized, sonicated, centrifuged (15,000 rpm, 5 min, 2 degrees C) and the supernatant injected into an Inertsil CN-3 column (4.6 mm x 150 mm, 5 microm) using 64:35:1 (v/v/v) water-methanol-triethylamine (pH 4.8), flow rate 1 ml/min, 25 degrees C. Imatinib eluted at 7.5 min (268 nm). Linearity: 0.1-50 microg/ml; precision, accuracy, inter- and intra-day variability was within 15%. Recovery was above 95% (plasma), 80% (brain) and 90% (kidney, liver, spleen). Imatinib tissue concentrations were 6-8 folds higher than plasma except brain, where the ratio decreased from 0.24 to 0.08 suggesting limited brain penetration, likely due to blood brain barrier efflux transporters. The extensive distribution supports the expansion of therapeutic applications.
    Matched MeSH terms: Piperazines/administration & dosage; Piperazines/pharmacokinetics*
  16. Man CN, Nor NM, Lajis R, Harn GL
    J Chromatogr A, 2009 Nov 20;1216(47):8426-30.
    PMID: 19853256 DOI: 10.1016/j.chroma.2009.10.016
    Sildenafil and its analogues (tadalafil and vardenafil) are phosphodiesterase type 5 inhibitors used in the treatment of male erectile dysfunction. Some dietary supplements, herbal preparations and food products which claim to enhance male sexual function have been found to be adulterated with these drugs. In this study, a gas chromatograph-mass spectrometer (GC-MS) assay was developed for identification of the drugs. In addition to good and short chromatographic separation that can be achieved within 6 min by using a short 10 m capillary column, no prior sample clean-up before GC-MS analysis was required, thus making this assay a cost saving and rapid method. Furthermore, the assay is specific as the identification of sildenafil, tadalafil and vardenafil were done by detection of molecular ions; m/z 474, 389 and 488, [corrected] respectively, and several other characteristic ions resulted from the mass fragmentation of individual molecules. Using our currently developed assay, sildenafil and its analogues were successfully identified in food and herbal matrices.
    Matched MeSH terms: Piperazines/analysis*; Piperazines/chemistry
  17. Wong AR, Rasool AH, Abidin NZ, Noor AR, Quah BS
    J Paediatr Child Health, 2006 Mar;42(3):147-8.
    PMID: 16509918
    Human Immunodeficiency Virus (HIV)-related pulmonary hypertension is a relatively rare disease that can affect HIV sufferers. This is almost always associated with a poor outcome and death. An 18 month-old girl, probably the youngest on record, was diagnosed to have pulmonary hypertension (PHT) and retrospectively found to have HIV infection. Sildenafil was used to control her PHT and she remains alive even after 2 years.
    Matched MeSH terms: Piperazines/administration & dosage*; Piperazines/therapeutic use
  18. Tan HM
    Int. J. Androl., 2000;23 Suppl 2:87-8.
    PMID: 10849506
    The quest for improving and maintaining sexual function has been going on since time immemorial. The advent of an effective oral drug, sildenafil, has brought about unprecedented open discussion on male erectile dysfunction, and gas accelerated the pace of development of new therapies for erectile dysfunction. New knowledge in the physiology of sexual function has enabled researchers to target drug treatment at the whole network of the central nervous system and the numerous cascadic enzymatic reactions leading to relaxation of the corporal smooth muscle. One of the brightest potential applications of future molecular technology in the study of erectile dysfuction is in the utilization of gene therapy.
    Matched MeSH terms: Piperazines/pharmacology; Piperazines/therapeutic use*
  19. Tan HM, Chin CM, Chua CB, Gatchalian E, Kongkanand A, Moh CL, et al.
    Asian J Androl, 2008 May;10(3):495-502.
    PMID: 18385912 DOI: 10.1111/j.1745-7262.2008.00388.x
    To evaluate the efficacy and tolerability of vardenafil, a phosphodiesterase type-5 (PDE-5) inhibitor, in men of Asian ethnicity with erectile dysfunction (ED).
    Matched MeSH terms: Piperazines/adverse effects; Piperazines/therapeutic use*
  20. Moo KS, Radhakrishnan S, Teoh M, Narayanan P, Bukhari NI, Segarra I
    Yao Xue Xue Bao, 2010 Jul;45(7):901-8.
    PMID: 20931790
    Imatinib is an efficacious anticancer drug with a spectrum of potential antitumour applications limited by poor biodistribution at therapeutic concentrations to the tissues of interest. We assess the pharmacokinetic and tissue distribution profile of imatinib in a liposome formulation. Its single dose (6.25 mg x kg(-1)) in a liposome formulation was administered iv to male mice. Imatinib concentration was measured in plasma, spleen, liver, kidney and brain using a HPLC assay. Non-compartmental pharmacokinetic approach was used to assess the disposition parameters. The plasma disposition profile was biphasic with a plateau-like second phase. The AUC(0-->infinity) was 11.24 microg x h x mL(-1), the elimination rate constant (k(el)) was 0.348 h(-1) and the elimination half life (t(1/2)) was 2.0 h. The mean residence time (MRT) was 2.59 h, V(SS) was 1.44 L x kg(-1) and clearance was 0.56 L x h x kg(-1). Liver achieved the highest tissue exposure: CMAX = 18.72 microg x mL(-1); AUC(0-->infinity)= 58.18 microg x h x mL(-1) and longest t(1/2) (4.29 h) and MRT (5.31 h). Kidney and spleen AUC(0-->infinity) were 47.98 microg x h x mL(-1) and 23.46 microg x h x mL(-1), respectively. Half-life was 1.83 h for the kidney and 3.37 h for the spleen. Imatinib penetrated into the brain reaching approximately 1 microg x g(-1). Upon correction by organ blood flow the spleen showed the largest uptake efficiency. Liposomal imatinib presented extensive biodistribution. The drug uptake kinetics showed mechanism differences amongst the tissues. These findings encourage the development of novel imatinib formulations to treat other cancers.
    Matched MeSH terms: Piperazines/administration & dosage; Piperazines/blood; Piperazines/pharmacokinetics*
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