Displaying publications 1 - 20 of 28 in total

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  1. Usman A, Razak IA, Fun HK, Chantrapromma S, Zhang Y, Xu JH
    Acta Crystallogr C, 2002 Feb;58(Pt 2):o59-62.
    PMID: 11828108
    In the syn- and anticlinal isomers of the title compound, C(22)H(18)N(2)O(6), the indole moiety is not completely planar, with the pyrrolidine ring being distorted very slightly towards a conformation intermediate between half-chair and envelope. The molecular and packing structures in the crystals of these isomers are stabilized by C-H...O interactions.
    Matched MeSH terms: Pyrrolidines
  2. Usman A, Razak IA, Chantrapromma S, Fun HK, Ray JK, Das Adhikari S, et al.
    Acta Crystallogr C, 2001 Dec;57(Pt 12):1441-2.
    PMID: 11740111
    In the title compound, C20H20FNO5S, the pyrrolidine ring adopts an envelope conformation. The fluorophenyl and thiophene rings are individually planar. The molecular and crystal structures are stabilized by intra- and intermolecular C-H...O interactions.
    Matched MeSH terms: Pyrrolidines
  3. Dutta S, Singhal S, Shah R, Charan J, Dhingra S, Haque M
    Expert Opin Drug Saf, 2023;22(12):1237-1251.
    PMID: 37526060 DOI: 10.1080/14740338.2023.2243217
    BACKGROUND: Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant.

    METHODS: An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms 'Daridorexant,' 'RCT,' 'Insomnia' trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively.

    RESULTS: Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), p = 0.36; I2 = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), p = 0.22; I2 = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), p = 0.82, I2 = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), p = 0.72, I2 = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one.

    CONCLUSION: Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia.

    PROSPERO: The registration number is CRD42022335233.

    CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).

    Matched MeSH terms: Pyrrolidines/adverse effects
  4. Suhud K, Heng LY, Hasbullah SA, Ahmad M, Kassim MB
    Acta Crystallogr E Crystallogr Commun, 2015 Apr 1;71(Pt 4):o225-6.
    PMID: 26029426 DOI: 10.1107/S2056989015003813
    In the title compound, C13H16N2O2S, the pyrrolidine ring has a twisted conformation on the central -CH2-CH2- bond. Its mean plane is inclined to the 4-meth-oxy-benzoyl ring by 72.79 (15)°. In the crystal, mol-ecules are linked by N-H⋯O and C-H⋯O hydrogen bonds to the same O-atom acceptor, forming chains along [001]. The chains are linked via slipped parallel π-π inter-actions [inter-centroid distance = 3.7578 (13) Å], forming undulating slabs parallel to (100).
    Matched MeSH terms: Pyrrolidines
  5. Mohammat MF, Shaameri Z, Hamzah AS
    Molecules, 2009;14(1):250-6.
    PMID: 19136912 DOI: 10.3390/molecules14010250
    Some novel 2,3-dioxo-5-(substituted)-arylpyrroles have been synthesized. Among these, pyrrolidine compound 1b was converted to 2,3-dioxo-5-aryl pyrrolidine 2b. Finally a set of hydrazone derivatives was obtained from the reaction of 2b with various hydrazine salts. The structures of all the new synthesized compounds were confirmed by elemental analyses, IR and 1H-NMR spectra.
    Matched MeSH terms: Pyrrolidines/chemical synthesis*; Pyrrolidines/chemistry
  6. Wei AC, Ali MA, Yoon YK, Ismail R, Choon TS, Kumar RS
    Bioorg Med Chem Lett, 2013 Mar 1;23(5):1383-6.
    PMID: 23352268 DOI: 10.1016/j.bmcl.2012.12.069
    A series of fourteen dispiropyrrolidines were synthesized using [3+2]-cycloaddition reactions and were screened for their antimycobacterial activity against Mycobacterium tuberculosis H(37)Rv in HTS (High Throughput Screen). Most of the compounds showed moderate to good activity with MIC of less than 20 μM. Compound 4'-(4-bromophenyl)-1'-methyldispiro[acenaphthylene-1,2'-pyrrolidine-3',2″-indane]-2,1″(1H)-dione (4c) was found to be the most active with MIC of 12.50 μM.
    Matched MeSH terms: Pyrrolidines/chemical synthesis*; Pyrrolidines/pharmacology; Pyrrolidines/chemistry
  7. Arahman N, Mulyati S, Fahrina A, Muchtar S, Yusuf M, Takagi R, et al.
    Molecules, 2019 Nov 13;24(22).
    PMID: 31766222 DOI: 10.3390/molecules24224099
    The removal of impurities from water or wastewater by the membrane filtration process has become more reliable due to good hydraulic performance and high permeate quality. The filterability of the membrane can be improved by having a material with a specific pore structure and good hydrophilic properties. This work aims at preparing a polyvinylidene fluoride (PVDF) membrane incorporated with phospholipid in the form of a 2-methacryloyloxyethyl phosphorylcholine, polymeric additive in the form of polyvinylpyrrolidone, and its combination with inorganic nanosilica from a renewable source derived from bagasse. The resulting membrane morphologies were analyzed by using scanning electron microscopy. Furthermore, atomic force microscopy was performed to analyze the membrane surface roughness. The chemical compositions of the resulting membranes were identified using Fourier transform infrared. A lab-scale cross-flow filtration system module was used to evaluate the membrane's hydraulic and separation performance by the filtration of humic acid (HA) solution as the model contaminant. Results showed that the additives improved the membrane surface hydrophilicity. All modified membranes also showed up to five times higher water permeability than the pristine PVDF, thanks to the improved structure. Additionally, all membrane samples showed HA rejections of 75-90%.
    Matched MeSH terms: Pyrrolidines/chemistry
  8. Wei AC, Ali MA, Yoon YK, Ismail R, Choon TS, Kumar RS, et al.
    Bioorg Med Chem Lett, 2012 Aug 1;22(15):4930-3.
    PMID: 22749825 DOI: 10.1016/j.bmcl.2012.06.047
    A series of twelve dispiropyrrolidines were synthesized using [3+2]-cycloaddition reactions. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H(37)Rv and INH resistant M. tuberculosis strains using agar dilution method, four of them showed good activity with MIC of less than 1 μM. Compound 4'-[5-(4-fluorophenyl)pyridin-3-yl]-1'-methyldispiro[indan-2,2' pyrrolidine-3',2″-indan]-1,3,1″-trione (4b) was found to be the most active with MIC of 0.1215 and 5.121 μM, respectively.
    Matched MeSH terms: Pyrrolidines/chemical synthesis*; Pyrrolidines/pharmacology; Pyrrolidines/chemistry*
  9. Kia Y, Osman H, Suresh Kumar R, Basiri A, Murugaiyah V
    Bioorg Med Chem Lett, 2014 Apr 1;24(7):1815-9.
    PMID: 24594354 DOI: 10.1016/j.bmcl.2014.02.019
    Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 1.68 to 21.85 μM, wherein compounds 8d and 8j were found to be most active inhibitors against AChE and BChE with IC50 values of 1.68 and 2.75 μM, respectively. Molecular modeling simulation on Torpedo californica AChE and human BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes.
    Matched MeSH terms: Pyrrolidines/chemical synthesis; Pyrrolidines/pharmacology*; Pyrrolidines/chemistry
  10. Almansour AI, Kumar RS, Beevi F, Shirazi AN, Osman H, Ismail R, et al.
    Molecules, 2014 Jul 10;19(7):10033-55.
    PMID: 25014532 DOI: 10.3390/molecules190710033
    A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 μM) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-α-Phenyl substituted spiro-pyrrolidine derivatives (5a-n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a-n, a number of derivatives including 6a-c and 6i-m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds in three classes, 6a, 6b, and 6m, were found to be the most potent derivatives showing 64%, 87%, and 74% antiproliferative activity in MDA-MB-231, SK-OV-3, and CCRF-CEM cells, respectively. Compound 6b showed an IC50 value of 3.6 mM in CCRF-CEM cells. These data suggest the potential antiproliferative activity of spiro-pyrrolidines/pyrrolizines.
    Matched MeSH terms: Pyrrolidines/chemical synthesis*; Pyrrolidines/pharmacology*
  11. Sim KM, Mak CN, Ho LP
    J Asian Nat Prod Res, 2009 Aug;11(8):757-60.
    PMID: 20183320 DOI: 10.1080/10286020903058933
    A new amide alkaloid, N-(3',4',5'-trimethoxy-cis-cinnamoyl)pyrrolidine (1), named sarmentomicine was isolated from the ethanol extract of the leaves of Malayan Piper sarmentosum, together with two known phenylpropanoids. Their structures were elucidated on the basis of spectroscopic analysis.
    Matched MeSH terms: Pyrrolidines/isolation & purification*; Pyrrolidines/chemistry
  12. Ali MA, Ismail R, Choon TS, Yoon YK, Wei AC, Pandian S, et al.
    Bioorg Med Chem Lett, 2010 Dec 1;20(23):7064-6.
    PMID: 20951037 DOI: 10.1016/j.bmcl.2010.09.108
    Series of pyrolidine analogues were synthesized and examined as acetylcholinesterase (AChE) inhibitors. Among the compounds, compounds 4k and 6k were the most potent inhibitors of the series. Compound 4k, showed potent inhibitory activity against acetyl cholinesterase enzyme with IC(50) 0.10 μmol/L. Pyrolidine analogues might be potential acetyl cholinesterase agents for AD.
    Matched MeSH terms: Pyrrolidines/chemical synthesis*; Pyrrolidines/pharmacology*
  13. Najim N, Bathich Y, Zain MM, Hamzah AS, Shaameri Z
    Molecules, 2010 Dec 17;15(12):9340-53.
    PMID: 21169884 DOI: 10.3390/molecules15129340
    The aim of this study was to investigate the in vitro cellular activity of novel spiroisoxazoline type compounds against normal and cancer cell lines from lung tissue (Hs888Lu), neuron-phenotypic cells (SH-SY5Y), neuroblastoma (SH-SY5Y), human histiocytic lymphoma (U937), lung cancer (A549), and leukaemia (HL-60). Our bioassay program revealed that the spiroisoxazoline type compounds show cytotoxicity only in lymphoma cell lines, which is in contrast with the pyrrolidine precursor of these spiroisoxazoline compounds, where significant cytotoxicity is seen in all normal and cancer cell lines. These data suggest a tumour-specific mechanism of action. In addition these data also show that spiroisoxazoline compounds are non-toxic in the human neuronphenotypic neuroblastoma SH-SY5Y cell line, and furthermore that they might protect cells from neurodegenerative disease.
    Matched MeSH terms: Pyrrolidines/pharmacology*; Pyrrolidines/chemistry*
  14. Boudriga S, Haddad S, Murugaiyah V, Askri M, Knorr M, Strohmann C, et al.
    Molecules, 2020 Apr 23;25(8).
    PMID: 32340203 DOI: 10.3390/molecules25081963
    A novel one-pot [3+2]-cycloaddition reaction of (E)-3-arylidene-1-phenyl-succinimides, cyclic 1,2-diketones (isatin, 5-chloro-isatin and acenaphtenequinone), and diverse α-aminoacids such as 2-phenylglycine or sarcosine is reported. The reaction provides succinimide-substituted dispiropyrrolidine derivatives with high regio- and diastereoselectivities under mild reaction conditions. The stereochemistry of these N-heterocycles has been confirmed by four X-ray diffraction studies. Several synthetized compounds show higher inhibition on acetylcholinesterase (AChE) than butyrylcholinesterase (BChE). Of the 17 synthesized compounds tested, five exhibit good AChE inhibition with IC50 of 11.42 to 22.21 µM. A molecular docking study has also been undertaken for compound 4n possessing the most potent AChE inhibitory activity, disclosing its binding to the peripheral anionic site of AChE enzymes.
    Matched MeSH terms: Pyrrolidines/pharmacology*; Pyrrolidines/chemistry*
  15. Basiri A, Abd Razik BM, Ezzat MO, Kia Y, Kumar RS, Almansour AI, et al.
    Bioorg Chem, 2017 12;75:210-216.
    PMID: 28987876 DOI: 10.1016/j.bioorg.2017.09.019
    Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, which affected 35 million people in the world. The most practiced approach to improve the life expectancy of AD patients is to increase acetylcholine neurotransmitter level at cholinergic synapses by inhibition of cholinesterase enzymes. A series of unreported piperidone grafted spiropyrrolidines 8(a-p) were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Therein, compounds 8h and 8l displayed more potent AChE enzyme inhibition than standard drug with IC50 values of 1.88 and 1.37 µM, respectively. Molecular docking simulations for 8l possessing the most potent AChE inhibitory activities, disclosed its interesting binding templates to the active site channel of AChE enzymes. These compounds are remarkable AChE inhibitors and have potential as AD drugs.
    Matched MeSH terms: Pyrrolidines/chemical synthesis; Pyrrolidines/metabolism; Pyrrolidines/pharmacology; Pyrrolidines/chemistry*
  16. Farhani S, Sulizah S, Siti Khalimah R, Jasrinjeet Kaur K, Nur Hidayah Z, Nur Athirah R, et al.
    Med J Malaysia, 2024 Jan;79(1):68-73.
    PMID: 38287760
    INTRODUCTION: Studies showed that vildagliptin can lower HbA1c levels by 0.8%-1%. However, there is limited data looking at vildagliptin use among suburban populations. The efficacy of vildagliptin use may differ among different populations, especially those with low socio-economic status. Thus, this study aimed to assess the HbA1c reduction after vildagliptin initiation, treatment patterns and the reason for its initiation among patients with type 2 diabetes mellitus attending outpatient clinics in Kuala Selangor District, Selangor.

    MATERIALS AND METHODS: This is a cross-sectional, retrospective study design. All patients who received vildagliptin in the Pharmacy Integrated Health System (PHIS) registry database from 2016 to 2021 were included as study samples. The exclusion criteria were being less than 18 years old and having type 1 diabetes mellitus. Patients' medical records were retrieved after sampling, and data were collected. One medical record was missing, thus SPSS analysis were performed on 144 vildagliptin users.

    RESULTS: In total, 84 females (58.3%) and 60 males (41.7%) with a mean age of 62.1 (±10.1) years were analysed in this study. Mean HbA1c pre-therapy was 8.5 ± 2.1%; while posttherapy 6 months demonstrated a mean HbA1c of 7.9 ± 1.8%. Use of vildagliptin alone or as an adjunct was associated with a mean reduction of 0.6% in HbA1c (p = 0.01). Factors influencing this HbA1c reduction were advancing age, specifically individuals aged 62 years and older (p = 0.02), patients who are already receiving insulin therapy (p=0.00) and those who express a willingness to commence insulin treatment during the counselling session prior to initiating the treatment plan (p = 0.00). Reasons for vildagliptin initiation documented by prescribers were non-insulin acceptance (n = 59, 40.97%), frequent hypoglycaemia (n = 6, 4.1%) and non-compliance with medications (n = 23, 15.9%). There was no association between demographic, medical background and reason for starting vildagliptin variables and HbA1c reduction (p < 0.001).

    CONCLUSION: This study showed that initiating vildagliptin alone or as an adjunct therapy significantly reduced HbA1c and is beneficial for uncontrolled diabetes patients. While advancing age, concurrent administration of insulin and the patients' willingness to accept insulin treatment prior to the commencement of therapy were the factors that influenced HbA1c reduction among patients receiving vildagliptin therapy, we recommend primary care providers prioritise all of the significant variables discovered before initiating vildagliptin for their patients.

    Matched MeSH terms: Pyrrolidines/adverse effects; Pyrrolidines/therapeutic use
  17. Kia Y, Osman H, Kumar RS, Basiri A, Murugaiyah V
    Bioorg Med Chem, 2014 Feb 15;22(4):1318-28.
    PMID: 24461561 DOI: 10.1016/j.bmc.2014.01.002
    One pot, three-component reaction of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with isatin and sarcosine in molar ratios of 1:1:1 and 1:2:2 furnished to mono- and bis-spiropyrrolidine heterocyclic hybrids comprising functionalized piperidine, pyrrolidine and oxindole structural motifs. Both mono and bis-spiropyrrolidines displayed good inhibitory activity against acetylcholinesterase (AChE) with IC₅₀ values of 2.36-9.43 μM. For butyrylcholinesterase (BChE), mono-cycloadducts in series 8 with IC₅₀ values of lower than 10 μM displayed better inhibitory activities than their bis-cycloadduct analogs in series 9 with IC₅₀ values of 7.44-19.12 μM. The cycloadducts 9j and 8e were found to be the most potent AChE and BChE inhibitors with IC₅₀ values of 2.35 and 3.21 μM, respectively. Compound 9j was found to be competitive inhibitor of AChE while compound 8e was a mixed-mode inhibitor of BChE with calculated Ki values of 2.01 and 6.76 μM, respectively. Molecular docking on Torpedo californica AChE and human BChE showed good correlation between IC₅₀ values and free binding energy values of the synthesized compounds docked into the active site of the enzymes.
    Matched MeSH terms: Pyrrolidines/chemical synthesis; Pyrrolidines/metabolism; Pyrrolidines/chemistry*
  18. Gorajana A, Ying CC, Shuang Y, Fong P, Tan Z, Gupta J, et al.
    Curr Drug Deliv, 2013 Jun;10(3):309-16.
    PMID: 23360246
    Dapivirine, formerly known as TMC 120, is a poorly-water soluble anti-HIV drug, currently being developed as a vaginal microbicide. The clinical use of this drug has been limited due to its poor solubility. The aim of this study was to design solid dispersion systems of Dapivirine to improve its solubility. Solid dispersions were prepared by solvent and fusion methods. Dapivirine release from the solid dispersion system was determined by conducting in-vitro dissolution studies. The physicochemical characteristics of the drug and its formulation were studied using Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). A significant improvement in drug dissolution rate was observed with the solid dispersion systems. XRD, SEM and DSC results indicated the transformation of pure Dapivirine which exists in crystalline form into an amorphous form in selected solid dispersion formulations. FTIR and HPLC analysis confirmed the absence of drug-excipient interactions. Solid dispersion systems can be used to improve the dissolution rate of Dapivirine. This improvement could be attributed to the reduction or absence of drug crystallinity, existence of drug particles in an amorphous form and improved wettability of the drug.
    Matched MeSH terms: Pyrrolidines/chemistry
  19. Almansour AI, Kumar RS, Arumugam N, Basiri A, Kia Y, Ali MA, et al.
    Molecules, 2015 Jan 29;20(2):2296-309.
    PMID: 25642838 DOI: 10.3390/molecules20022296
    A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC50 value of 1.57 µM against acethylcholinesterase (AChE). Molecular docking simulation for the most active compound was employed with the aim of disclosing its binding mechanism to the active site of AChE receptor.
    Matched MeSH terms: Pyrrolidines/chemical synthesis*
  20. Johari SA, Mohtar M, Mohammad SA, Sahdan R, Shaameri Z, Hamzah AS, et al.
    Biomed Res Int, 2015;2015:823829.
    PMID: 25710030 DOI: 10.1155/2015/823829
    28 new pyrrolidine types of compounds as analogues for natural polyhydroxy alkaloids of codonopsinine were evaluated for their anti-MRSA activity using MIC and MBC value determination assay against a panel of S. aureus isolates. One pyrrolidine compound, MFM 501, exhibited good inhibitory activity with MIC value of 15.6 to 31.3 μg/mL against 55 S. aureus isolates (43 MRSA and 12 MSSA isolates). The active compound also displayed MBC values between 250 and 500 μg/mL against 58 S. aureus isolates (45 MRSA and 13 MSSA isolates) implying that MFM 501 has a bacteriostatic rather than bactericidal effect against both MRSA and MSSA isolates. In addition, MFM 501 showed no apparent cytotoxicity activity towards three normal cell lines (WRL-68, Vero, and 3T3) with IC50 values of >625 µg/mL. Selectivity index (SI) of MFM 501 gave a value of >10 suggesting that MFM 501 is significant and suitable for further in vivo investigations. These results suggested that synthetically derived intermediate compounds based on natural products may play an important role in the discovery of new anti-infective agents against MRSA.
    Matched MeSH terms: Pyrrolidines/administration & dosage*; Pyrrolidines/chemistry
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