MyMedR

Displaying publications 41 - 50 of 50 in total

Abstract:

Sort:

Synthesis of quinoline derivatives as diabetic II inhibitors and molecular docking studies

Taha M, Sultan S, Imran S, Rahim F, Zaman K, Wadood A, et al.

Bioorg Med Chem, 2019 09 15;27(18):4081-4088.
PMID: 31378594 DOI: 10.1016/j.bmc.2019.07.035

In searchof the potenttherapeutic agent as an α-glucosidase inhibitor, we have synthesized twenty-five analogs (1-25) of quinoline-based Schiff bases as an inhibitoragainst α-glucosidase enzyme under positive control acarbose (IC50 = 38.45 ± 0.80 µM). From the activity profile it was foundthat analogs 1, 2, 3, 4, 11, 12 and 20with IC50values 12.40 ± 0.40, 9.40 ± 0.30, 14.10 ± 0.40, 6.20 ± 0.30, 14.40 ± 0.40, 7.40 ± 0.20 and 13.20 ± 0.40 µMrespectively showed most potent inhibition among the series even than standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Here in the present study analog 4 (IC50 = 6.20 ± 0.30 µM) was found with many folds better α-glucosidase inhibitory activity than the reference drug. Eight analogs like 5, 7, 8, 16, 17, 22, 24 and 25 among the whole series displayed less than 50% inhibition. The substituents effects on phenyl ring thereby superficially established through SAR study. Binding interactions of analogs and the active site of ligands proteins were confirmed through molecular docking study. Spectroscopic techniques like 1H NMR, 13C NMR and ESIMS were used for characterization.

Matched MeSH terms: Quinolines/chemical synthesis*
Molecular hybridization conceded exceptionally potent quinolinyl-oxadiazole hybrids through phenyl linked thiosemicarbazide antileishmanial scaffolds: In silico validation and SAR studies

Taha M, Ismail NH, Ali M, Rashid U, Imran S, Uddin N, et al.

Bioorg Chem, 2017 04;71:192-200.
PMID: 28228228 DOI: 10.1016/j.bioorg.2017.02.005

The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover a novel series of compounds 6-23 based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal potential. The most potent compound (23, IC50=0.10±0.001μM) among the series was found ∼70 times more lethal than the standard drug. The current series 6-23 conceded in the development of fourteen (14) extraordinarily active compounds against leishmaniasis. In silico analysis were also performed to probe the mode of action while all the compounds structure were established by NMR and Mass spectral analysis.

Matched MeSH terms: Quinolines/pharmacology; Quinolines/chemistry
Synthesis and study of the α-amylase inhibitory potential of thiadiazole quinoline derivatives

Taha M, Tariq Javid M, Imran S, Selvaraj M, Chigurupati S, Ullah H, et al.

Bioorg Chem, 2017 10;74:179-186.
PMID: 28826047 DOI: 10.1016/j.bioorg.2017.08.003

α-Amylase is a target for type-2 diabetes mellitus treatment. However, small molecule inhibitors of α-amylase are currently scarce. In the course of developing small molecule α-amylase inhibitors, we designed and synthesized thiadiazole quinoline analogs (1-30), characterized by different spectroscopic techniques such as 1HNMR and EI-MS and screened for α-amylase inhibitory potential. Thirteen analogs 1, 2, 3, 4, 5, 6, 22, 23, 25, 26, 27, 28 and 30 showed outstanding α-amylase inhibitory potential with IC50 values ranges between 0.002±0.60 and 42.31±0.17μM which is many folds better than standard acarbose having IC50 value 53.02±0.12μM. Eleven analogs 7, 9, 10, 11, 12, 14, 15, 17, 18, 19 and 24 showed good to moderate inhibitory potential while seven analogs 8, 13, 16, 20, 21 and 29 were found inactive. Our study identifies novel series of potent α-amylase inhibitors for further investigation. Structure activity relationship has been established.

Matched MeSH terms: Quinolines/chemical synthesis; Quinolines/pharmacology*; Quinolines/chemistry
Inhibitory effect of the extract from Sonchus olearleu on the formation of carcinogenic heterocyclic aromatic amines during the pork cooking

Teng H, Chen Y, Lin X, Lv Q, Chai TT, Wong FC, et al.

Food Chem Toxicol, 2019 Jul;129:138-143.
PMID: 31034934 DOI: 10.1016/j.fct.2019.04.043

The aim of this study was to assess the inhibitory effects of Sonchus olearleu extract on the generation of heterocyclic amines in roasted pork patties cooked by pan-frying. All samples were cooked for two different durations (45 min and 105 min) under 200 °C and 230 °C. 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-ami- no-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinox-aline (4,8-DiMeIQx), harman, and norharman were detected and quantified. In patties cooked at 230 °C for 105 min, S. olearleu extract (0.5%) significantly inhibited the formation of IQ, harman, and norharman by 39%, 67%, and 63%, respectively. In contrast to IQ, the levels of harman and norharman were significantly reduced by the extracts tested. However, no such effects were observed for MeIQx and 4, 8-DiMeIQx. Notably, the inhibitory effect on heterocyclic amines is significantly correlated with the antioxidant potential and total phenolic content of S. olearleu extract.

Matched MeSH terms: Quinolines
Current progress in antimalarial pharmacotherapy and multi-target drug discovery

Tibon NS, Ng CH, Cheong SL

Eur J Med Chem, 2020 Feb 15;188:111983.
PMID: 31911292 DOI: 10.1016/j.ejmech.2019.111983

Discovery and development of antimalarial drugs have long been dominated by single-target therapy. Continuous effort has been made to explore and identify different targets in malaria parasite crucial for the malaria treatment. The single-target drug therapy was initially successful, but it was later supplanted by combination therapy with multiple drugs to overcome drug resistance. Emergence of resistant strains even against the combination therapy has warranted a review of current antimalarial pharmacotherapy. This has led to the development of the new concept of covalent biotherapy, in which two or more pharmacophores are chemically bound to produce hybrid antimalarial drugs with multi-target functionalities. Herein, the review initially details the current pharmacotherapy for malaria as well as the conventional and novel targets of importance identified in the malaria parasite. Then, the rationale of multi-targeted therapy for malaria, approaches taken to develop the multi-target antimalarial hybrids, and the examples of hybrid molecules are comprehensively enumerated and discussed.

Matched MeSH terms: Quinolines/pharmacology*; Quinolines/chemistry
Development of LC-MS/MS method and application to bioequivalence study of a light sensitive drug montelukast

Wong EYL, Loh GOK, Tan YTF, Peh KK

Drug Dev Ind Pharm, 2021 Feb;47(2):197-206.
PMID: 33300818 DOI: 10.1080/03639045.2020.1862177

OBJECTIVE: The aim of the study was to develop a simple, highthroughput and sensitive LC-MS/MS method and apply to a bioequivalence study of montelukast, a light sensitive drug.
METHOD: The effects of organic modifiers in mobile phase, protein precipitation agent to plasma sample ratio, and light on montelukast stability in unprocessed and processed human plasma, were evaluated. Validation was conducted in accordance with European Medicines Agency Guideline on bioanalytical method validation.
RESULTS: No interference peak was observed when acetonitrile was used as an organic modifier. Acetonitrile to plasma ratio of 4:1 produced clean plasma sample. Approximately 3 % of cis isomer was detected in unprocessed plasma samples while 21 % of cis isomer was detected in processed plasma samples after exposing to fluorescent light for 24h. The standard calibration curve was linear over 3.00-1200.00 ng/mL. All method validation parameters were within the acceptance criteria.
CONCLUSION: The validated method was successfully applied to a bioequivalence study of two montelukast formulations involving 24 healthy Malaysian volunteers. The light stability of a light sensitive drug in unprocessed and processed human plasma samples should be studied prior to pharmacokinetic/bioequivalence studies. Measures could then be taken to protect the analyte in human plasma from light degradation.

Matched MeSH terms: Quinolines/pharmacology*; Quinolines/chemistry
Fulltext Moxifloxacin-warfarin interaction

Yew KL, Lee WC

Med J Malaysia, 2012 Aug;67(4):420-1.
PMID: 23082454 MyJurnal
Matched MeSH terms: Quinolines/adverse effects*
Fulltext Montelukast sodium-induced hypomania

Zainal, N.Z., Tan, T.Y

Malaysian Journal of Psychiatry, 2015;24(1):96-98.
MyJurnal

Objective: A rare case of induced hypomania was reported. Method: Patient was a 78-year-old Indian female with squamous cell carcinoma of the nasal septum, childhood bronchial asthma and underlying bipolar disorder. Her bipolar disorder is currently in remission. She developed hypomanic symptoms after one week of initiation of montelukast sodium for treatment of acute exacerbation of bronchial asthma. Result: Her hypomanic symptoms improved after stopping usage of montelukast sodium. Conclusion: Montelukast sodium likely had induced hypomania in this patient.

Matched MeSH terms: Quinolines
Fulltext Zinc/Aluminium⁻Quinclorac Layered Nanocomposite Modified Multi-Walled Carbon Nanotube Paste Electrode for Electrochemical Determination of Bisphenol A

Zainul R, Abd Azis N, Md Isa I, Hashim N, Ahmad MS, Saidin MI, et al.

Sensors (Basel), 2019 Feb 22;19(4).
PMID: 30813385 DOI: 10.3390/s19040941

This paper presents the application of zinc/aluminium-layered double hydroxide-quinclorac (Zn/Al-LDH-QC) as a modifier of multiwalled carbon nanotubes (MWCNT) paste electrode for the determination of bisphenol A (BPA). The Zn/Al-LDH-QC/MWCNT morphology was examined by a transmission electron microscope and a scanning electron microscope. Electrochemical impedance spectroscopy was utilized to investigate the electrode interfacial properties. The electrochemical responses of the modified electrode towards BPA were thoroughly evaluated by using square-wave voltammetry technique. The electrode demonstrated three linear plots of BPA concentrations from 3.0 × 10-8⁻7.0 × 10-7 M (R² = 0.9876), 1.0 × 10-6⁻1.0 × 10-5 M (R² = 0.9836) and 3.0 × 10-5⁻3.0 × 10-4 M (R² = 0.9827) with a limit of detection of 4.4 × 10-9 M. The electrode also demonstrated good reproducibility and stability up to one month. The presence of several metal ions and organic did not affect the electrochemical response of BPA. The electrode is also applicable for BPA determination in baby bottle and mineral water samples with a range of recovery between 98.22% and 101.02%.

Matched MeSH terms: Quinolines
Synthesis, in vitro antiurease, in vivo antinematodal activity of quinoline analogs and their in-silico study

Zaman K, Rahim F, Taha M, Sajid M, Hayat S, Nawaz M, et al.

Bioorg Chem, 2021 10;115:105199.
PMID: 34329995 DOI: 10.1016/j.bioorg.2021.105199

Synthesis of quinoline analogs and their urease inhibitory activities with reference to the standard drug, thiourea (IC50 = 21.86 ± 0.40 µM) are presented in this study. The inhibitory activity range is (IC50 = 0.60 ± 0.01 to 24.10 ± 0.70 µM) which displayed that it is most potent class of urease inhibitor. Analog 1-9, and 11-13 emerged with many times greater antiurease potential than thiourea, in which analog 1, 2, 3, 4, 8, 9, and 11 (IC50 = 3.50 ± 0.10, 7.20 ± 0.20, 1.30 ± 0.10, 2.30 ± 0.10, 0.60 ± 0.01, 1.05 ± 0.10 and 2.60 ± 0.10 µM respectively) were appeared the most potent ones among the series. In this context, most potent analogs such as 1, 3, 4, 8, and 9 were further subjected for their in vitro antinematodal study against C. elegans to examine its cytotoxicity under positive control of standard drug, Levamisole. Consequently, the cytotoxicity profile displayed that analogs 3, 8, and 9 were found with minimum cytotoxic outline at higher concentration (500 µg/mL). All analogs were characterized through 1H NMR, 13C NMR and HR-EIMS. The protein-ligand binding interaction for most potent analogs was confirmed via molecular docking study.

Matched MeSH terms: Quinolines/chemical synthesis; Quinolines/pharmacology*; Quinolines/chemistry