Displaying publications 21 - 40 of 799 in total

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  1. New cytotoxic rosamine derivatives selectively accumulate in the mitochondria of cancer cells
    Lim SH, Wu L, Burgess K, Lee HB
    Anticancer Drugs, 2009 Jul;20(6):461-8.
    PMID: 19387338 DOI: 10.1097/CAD.0b013e32832b7bee
    Conventional cytotoxic anticancer drugs that target all rapidly dividing cells are nonselective in their mechanism of action, because they disrupt essential components that are crucial to both malignant and proliferating normal cells. Instead, targeting cellular functions that are distinctly different between normal and cancer cells may provide a basis for selective killing of tumor cells. One such strategy that is still largely unexplored is to utilize the relatively higher negative mitochondrial membrane potential in carcinoma cells compared with adjacent normal epithelial cells to enhance accumulation and retention of cytotoxic lipophilic cations in the former. In this study, the anticancer activities of a new class of rosamines with cyclic amine substituents and their structure-activity relationships were investigated. From an in-vitro cell growth inhibition assay, 14 of the rosamines inhibited the growth of human leukemia HL-60 cells by 50% at micromolar or lower concentrations. Derivatives containing hydrophilic substituents had less potent activity, whereas aryl substitution at the meso position conferred extra activity with thiofuran and para-iodo aryl substitutions being the most potent. In addition, both compounds were at least 10-fold more cytotoxic than rhodamine 123 against a panel of cell lines of different tissue origin and similar to rhodamine 123, exhibited more cytotoxicity against cancer cells compared with immortalized normal epithelial cells of the same organ type. In subsequent experiments, the para-iodo aryl substituted rosamine was found to localize exclusively within the mitochondria and induced apoptosis as the major mode of cell death. Our results suggest that these compounds offer potential for the design of mitochondria-targeting agents that either directly kill or deliver cytotoxic drugs to selectively kill cancer cells.
    Matched MeSH terms: Molecular Structure
  2. Fulltext Cyclophilin A as a target in the treatment of cytomegalovirus infections
    A Abdullah A, Abdullah R, A Nazariah Z, N Balakrishnan K, Firdaus J Abdullah F, A Bala J, et al.
    Antivir Chem Chemother, 2018;26:2040206618811413.
    PMID: 30449131 DOI: 10.1177/2040206618811413
    BACKGROUND: Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity.

    METHODS: Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins.

    RESULTS: Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug.

    CONCLUSION: Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.

    Matched MeSH terms: Molecular Structure
  3. Synthesis, Structure, and Anticancer Activity of Symmetrical and Non-symmetrical Silver(I)-N-Heterocyclic Carbene Complexes
    Atif M, Bhatti HN, Haque RA, Iqbal MA, Ahamed Khadeer MB, Majid AMSA
    Appl Biochem Biotechnol, 2020 Jul;191(3):1171-1189.
    PMID: 32002729 DOI: 10.1007/s12010-019-03186-9
    Synthesis and anticancer studies of three symmetrically and non-symmetrically substituted silver(I)-N-Heterocyclic carbene complexes of type [(NHC)2-Ag]PF6 (7-9) and their respective (ligands) benzimidazolium salts (4-6) are described herein. Compound 5 and Ag-NHC-complex 7 were characterized by the single crystal X-ray diffraction technique. Structural studies for 7 showed that the silver(I) center has linear C-Ag-C coordination geometry (180.00(10)o). Other azolium and Ag-NHC analogues were confirmed by H1 and C13-NMR spectroscopy. The synthesized analogues were biologically characterized for in vitro anticancer activity against three cancer cell lines including human colorectal cancer (HCT 116), breast cancer (MCF-7), and erythromyeloblastoid leukemia (K-562) cell lines and in terms of in vivo acute oral toxicity (IAOT) in view of agility and body weight of female rats. In vitro anticancer activity showed the values of IC50 in range 0.31-17.9 μM in case of K-562 and HCT-116 cancer cell lines and 15.1-35.2 μM in case of MCF-7 while taking commercially known anticancer agents 5-fluorouracil, tamoxifen, and betulinic acid which have IC50 values 5.2, 5.5, and 17.0 μM, respectively. In vivo study revealed vigor and agility of all test animals which explores the biocompatibility and non-toxicity of the test analogues.
    Matched MeSH terms: Molecular Structure
  4. Synthesis of α-hydroxyphosphonates and their antioxidant properties
    Naidu KR, Kumar KS, Arulselvan P, Reddy CB, Lasekan O
    Arch Pharm (Weinheim), 2012 Dec;345(12):957-63.
    PMID: 23015406 DOI: 10.1002/ardp.201200192
    A series of α-hydroxyphosphonates were synthesized from the reaction of aldehyde (1) with triethylphosphite (2) in the presence of oxone and evaluated for their antioxidant properties against lipid peroxidation, reduced glutathione, superoxide dismutase, and catalase. The majority of the compounds showed promising antioxidant activity. Diethyl anthracen-9-yl (hydroxy) methylphosphonate (3n) is the most potent and biologically active compound against free radicals.
    Matched MeSH terms: Molecular Structure
  5. Bi-heterocyclic benzamides as alkaline phosphatase inhibitors: Mechanistic comprehensions through kinetics and computational approaches
    Abbasi MA, Nazir M, Ur-Rehman A, Siddiqui SZ, Hassan M, Raza H, et al.
    Arch Pharm (Weinheim), 2019 Mar;352(3):e1800278.
    PMID: 30624805 DOI: 10.1002/ardp.201800278
    Novel bi-heterocyclic benzamides were synthesized by sequentially converting 4-(1H-indol-3-yl)butanoic acid (1) into ethyl 4-(1H-indol-3-yl)butanoate (2), 4-(1H-indol-3-yl)butanohydrazide (3), and a nucleophilic 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazole-2-thiol (4). In a parallel series of reactions, various electrophiles were synthesized by reacting substituted anilines (5a-k) with 4-(chloromethyl)benzoylchloride (6) to afford 4-(chloromethyl)-N-(substituted-phenyl)benzamides (7a-k). Finally, the nucleophilic substitution reaction of 4 was carried out with newly synthesized electrophiles, 7a-k, to acquire the targeted bi-heterocyclic benzamides, 8a-k. The structural confirmation of all the synthesized compounds was done by IR, 1 H NMR, 13 C NMR, EI-MS, and CHN analysis data. The inhibitory effects of these bi-heterocyclic benzamides (8a-k) were evaluated against alkaline phosphatase, and all these molecules were identified as potent inhibitors relative to the standard used. The kinetics mechanism was ascribed by evaluating the Lineweaver-Burk plots, which revealed that compound 8b inhibited alkaline phosphatase non-competitively to form an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 1.15 μM. The computational study was in full agreement with the experimental records and these ligands exhibited good binding energy values. These molecules also exhibited mild cytotoxicity toward red blood cell membranes when analyzed through hemolysis. So, these molecules might be deliberated as nontoxic medicinal scaffolds to render normal calcification of bones and teeth.
    Matched MeSH terms: Molecular Structure
  6. A novel five-step synthetic route to 1,3,4-oxadiazole derivatives with potent α-glucosidase inhibitory potential and their in silico studies
    Iftikhar M, Shahnawaz, Saleem M, Riaz N, Aziz-Ur-Rehman, Ahmed I, et al.
    Arch Pharm (Weinheim), 2019 Dec;352(12):e1900095.
    PMID: 31544284 DOI: 10.1002/ardp.201900095
    A series of new N-aryl/aralkyl derivatives of 2-methyl-2-{5-(4-chlorophenyl)-1,3,4-oxadiazole-2ylthiol}acetamide were synthesized by successive conversions of 4-chlorobenzoic acid (a) into ethyl 4-chlorobenzoate (1), 4-chlorobenzoylhydrazide (2) and 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol (3), respectively. The required array of compounds (6a-n) was obtained by the reaction of 1,3,4-oxadiazole (3) with various electrophiles (5a-n) in the presence of DMF (N,N-dimethylformamide) and sodium hydroxide at room temperature. The structural determination of these compounds was done by infrared, 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, electron ionization mass spectrometry, and high-resolution electron ionization mass spectrometry analyses. All compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 6a, 6c-e, 6g, and 6i were found to be promising inhibitors of α-glucosidase with IC50 values of 81.72 ± 1.18, 52.73 ± 1.16, 62.62 ± 1.15, 56.34 ± 1.17, 86.35 ± 1.17, 52.63 ± 1.16 µM, respectively. Molecular modeling and ADME (absorption, distribution, metabolism, excretion) predictions supported the findings. The current synthesized library of compounds was achieved by utilizing very common raw materials in such a way that the synthesized compounds may prove to be promising drug leads.
    Matched MeSH terms: Molecular Structure
  7. Probing simple structural modification of α-mangostin on its cholinesterase inhibition and cytotoxicity
    Khaw KY, Kumar P, Yusof SR, Ramanathan S, Murugaiyah V
    Arch Pharm (Weinheim), 2020 Nov;353(11):e2000156.
    PMID: 32716578 DOI: 10.1002/ardp.202000156
    α-Mangostin has been reported to possess a broad range of pharmacological effects including potent cholinesterase inhibition, but the development of α-mangostin as a potential lead compound is impeded by its toxicity. The present study investigated the impact of simple structural modification of α-mangostin on its cholinesterase inhibitory activities and toxicity toward neuroblastoma and liver cancer cells. The dialkylated derivatives retained good acetylcholinesterase (AChE) inhibitory activities with IC50 values between 4.15 and 6.73 µM, but not butyrylcholinesterase (BChE) inhibitory activities, compared with α-mangostin, a dual inhibitor (IC50 : AChE, 2.48 µM; BChE, 5.87 µM). Dialkylation of α-mangostin produced AChE selective inhibitors that formed hydrophobic interactions at the active site of AChE. Interestingly, all four dialkylated derivatives of α-mangostin showed much lower cytotoxicity, being 6.4- to 9.0-fold and 3.8- to 5.5-fold less toxic than their parent compound on neuroblastoma and liver cancer cells, respectively. Likewise, their selectivity index was higher by 1.9- to 4.4-fold; in particular, A2 and A4 showed improved selectivity index compared with α-mangostin. Taken together, modification of the hydroxyl groups of α-mangostin at positions C-3 and C-6 greatly influenced its BChE inhibitory and cytotoxic but not its AChE inhibitory activities. These dialkylated derivatives are viable candidates for further structural modification and refinement, worthy in the search of new AChE inhibitors with higher safety margins.
    Matched MeSH terms: Molecular Structure
  8. TEOA, a triterpenoid from Actinidia eriantha, induces autophagy in SW620 cells via endoplasmic reticulum stress and ROS-dependent mitophagy
    Zhang D, Gao C, Li R, Zhang L, Tian J
    Arch Pharm Res, 2017 May;40(5):579-591.
    PMID: 28211011 DOI: 10.1007/s12272-017-0899-9
    2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62. Further analysis illustrated that TEOA promoted the phosphorylation of PERK and elF2α, followed by up-regulation of the downstream protein CHOP, suggesting the involvement of PERK/eIF2α/CHOP pathway and ER stress in TEOA-induced autophagy in SW620 cells. Meanwhile, TEOA-mediated PINK1, Parkin, ubiquitin and p62 activation revealed that TEOA induced specific autophagy-mitophagy in SW620 cells. Additionally, an antioxidant NAC attenuated the TEOA-induced mitophagy, indicating that TEOA triggers mitophagy via a ROS-dependent pathway. Collectively, our findings revealed a novel cellular mechanism of TEOA in the colon cancer cell line SW620, thus providing a molecular basis for developing TEOA into an anti-tumor candidate.
    Matched MeSH terms: Molecular Structure
  9. Flavonoids: promising natural compounds against viral infections
    Zakaryan H, Arabyan E, Oo A, Zandi K
    Arch Virol, 2017 Sep;162(9):2539-2551.
    PMID: 28547385 DOI: 10.1007/s00705-017-3417-y
    Flavonoids are widely distributed as secondary metabolites produced by plants and play important roles in plant physiology, having a variety of potential biological benefits such as antioxidant, anti-inflammatory, anticancer, antibacterial, antifungal and antiviral activity. Different flavonoids have been investigated for their potential antiviral activities and several of them exhibited significant antiviral properties in in vitro and even in vivo studies. This review summarizes the evidence for antiviral activity of different flavonoids, highlighting, where investigated, the cellular and molecular mechanisms of action on viruses. We also present future perspectives on therapeutic applications of flavonoids against viral infections.
    Matched MeSH terms: Molecular Structure
  10. Fulltext 4-(4-Bromophenyl)-thiazol-2-amine derivatives: synthesis, biological activity and molecular docking study with ADME profile
    Sharma D, Kumar S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2019 Dec;13(1):60.
    PMID: 31384808 DOI: 10.1186/s13065-019-0575-x
    In order to overcome the challenges of microbial resistance as well as to improve the effectiveness and selectivity of chemotherapeutic agents against cancer, a novel series of 4-(4-bromophenyl)-thiazol-2-amine derivatives was synthesized and its molecular structures were confirmed by physicochemical and spectral characteristics. The synthesized compounds were further evaluated for their in vitro antimicrobial activity using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. The antimicrobial activity results revealed that compound p2, p3, p4 and p6 exhibited promising antimicrobial activity that are comparable to standard norfloxacin (antibacterial) and fluconazole (antifungal). Anticancer screening results demonstrated that compound p2 was found to be the most active one against cancer cell line when compared to the rest of the compounds and comparable to the standard drug (5-fluorouracil). The molecular docking study demonstrated that compounds, p2, p3, p4 and p6 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and showed promising ADME properties.
    Matched MeSH terms: Molecular Structure
  11. Fulltext Synthesis, molecular modelling and biological significance of N-(4-(4-bromophenyl) thiazol-2-yl)-2-chloroacetamide derivatives as prospective antimicrobial and antiproliferative agents
    Sharma D, Kumar S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2019 Dec;13(1):46.
    PMID: 31384794 DOI: 10.1186/s13065-019-0564-0
    To combat the antimicrobial and anticancer drug resistance by pathogens and cancerous cells, efforts has been made to study the pharmacological activities of newly synthesized N-(4-(4-bromophenyl)thiazol-2-yl)-2-chloroacetamide derivatives. The molecular structures of the synthesized derivatives were confirmed by their physicochemical properties and spectroanalytical data (NMR, IR and elemental). The synthesized compounds were evaluated for their in vitro antimicrobial activity against bacterial (Gram positive and Gram negative) and fungal species using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. Molecular docking studies were carried out to study the binding mode of active compounds with receptor using Schrodinger v11.5. The antimicrobial activity results revealed that compounds d1, d2 and d3 have promising antimicrobial activity. Anticancer screening results indicated that compounds d6 and d7 were found to be the most active ones against breast cancer cell line. Furthermore, the molecular docking study demonstrated that compounds d1, d2, d3, d6 and d7 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and has the potential to be used as lead compounds for rational drug designing.
    Matched MeSH terms: Molecular Structure
  12. Fulltext Synthesis, anti-leishmanial and molecular docking study of bis-indole derivatives
    Taha M, Uddin I, Gollapalli M, Almandil NB, Rahim F, Farooq RK, et al.
    BMC Chem, 2019 Dec;13(1):102.
    PMID: 31410413 DOI: 10.1186/s13065-019-0617-4
    We have synthesized new series of bisindole analogs (1-27), characterized by 1HNMR and HR-EI-MS and evaluated for their anti-leishmanial potential. All compounds showed outstanding inhibitory potential with IC50 values ranging from 0.7 ± 0.01 to 13.30 ± 0.50 µM respectively when compared with standard pentamidine with IC50 value of 7.20 ± 0.20 µM. All analogs showed greater potential than standard except 10, 19 and 23 when compared with standard. Structure activity relationship has been also established for all compounds. Molecular docking studies were carried out to understand the binding interaction of active molecules.
    Matched MeSH terms: Molecular Structure
  13. Quantum mechanical tunnelling through the catalytic effects of A2451 ribosomal residue during a stepwise peptide bond formation
    Monajemi H, Md Zain S, Ishida T, Wan Abdullah WAT
    Biochem. Cell Biol., 2019 08;97(4):497-503.
    PMID: 30444637 DOI: 10.1139/bcb-2018-0220
    The search for the mechanism of ribosomal peptide bond formation is still ongoing. Even though the actual mechanism of peptide bod formation is still unknown, the dominance of proton transfer in this reaction is known for certain. Therefore, it is vital to take the quantum mechanical effects on proton transfer reaction into consideration; the effects of which were neglected in all previous studies. In this study, we have taken such effects into consideration using a semi-classical approach to the overall reaction mechanism. The M06-2X density functional with the 6-31++G(d,p) basis set was used to calculate the energies of the critical points on the potential energy surface of the reaction mechanism, which are then used in transition state theory to calculate the classical reaction rate. The tunnelling contribution is then added to the classical part by calculating the transmission permeability and tunnelling constant of the reaction barrier, using the numerical integration over the Boltzmann distribution for the symmetrical Eckart potential. The results of this study, which accounts for quantum effects, indicates that the A2451 ribosomal residue induces proton tunnelling in a stepwise peptide bond formation.
    Matched MeSH terms: Molecular Structure
  14. Platelet-activating factor (PAF) receptor binding antagonist activity of the methanol extracts and isolated flavonoids from Chromolaena odorata (L.) King and Robinson
    Ling SK, Pisar MM, Man S
    Biol Pharm Bull, 2007 Jun;30(6):1150-2.
    PMID: 17541171
    The leaf, stem and root extracts of Chromolaena odorata were evaluated for their effect on platelet-activating factor (PAF) receptor binding on rabbit platelets using 3H-PAF as a ligand. The leaf extract demonstrated high PAF receptor binding inhibitory activity of 79.2+/-2.1% at 18.2 microg/ml. A total of eleven flavonoids were subsequently isolated from the active leaf extract and evaluated for their effects on PAF receptor binding. Eight of the flavonoids exhibited >50% inhibition on the binding activity at 18.2 microg/ml. These flavonoids were identified as eriodictyol 7,4'-dimethyl ether, quercetin 7,4'-methyl ether, naringenin 4'-methyl ether, kaempferol 4'-methyl ether, kaempferol 3-O-rutinoside, taxifolin 4'-methyl ether, taxifolin 7-methyl ether and quercetin 4'-methyl ether. Their IC50 values ranged from 19.5 to 62.1 microM.
    Matched MeSH terms: Molecular Structure
  15. Simultaneous determination of atenolol and amiloride in pharmaceutical preparations by capillary zone electrophoresis with capacitively coupled contactless conductivity detection
    Al Azzam KM, Saad B, Aboul-Enein HY
    Biomed Chromatogr, 2010 Sep;24(9):948-53.
    PMID: 20082285 DOI: 10.1002/bmc.1390
    Capillary zone electrophoresis coupled with a capacitively coupled contactless conductivity detector (CE-C(4)D) has been employed for the determination of atenolol and amiloride in pharmaceutical formulations. Acetic acid (150 mm) was used as background electrolyte. The influence of several factors (detector excitation voltage and frequency, buffer concentration, applied voltage, capillary temperature and injection time) was studied. Non-UV-absorbing L-valine was used as internal standard; the analytes were all separated in less than 7 min. The separation was carried out in normal polarity mode at 28 degrees C, 25 kV and using hydrodynamic injection (25 s). The separation was effected in an uncoated fused-silica capillary (75 microm, i.d. x 52 cm). The CE-C(4)D method was validated with respect to linearity, limit of detection and quantification, accuracy, precision and selectivity. Calibration curves were linear over the range 5-250 microg/mL for the studied analytes. The relative standard deviations of intra- and inter-day migration times and corrected peak areas were less than 6.0%. The method showed good precision and accuracy and was successfully applied to the simultaneous determination of atenolol and amiloride in different pharmaceutical tablet formulations.
    Matched MeSH terms: Molecular Structure
  16. Simultaneous determination of atenolol, chlorthalidone and amiloride in pharmaceutical preparations by capillary zone electrophoresis with ultraviolet detection
    Al Azzam KM, Saad B, Aboul-Enein HY
    Biomed Chromatogr, 2010 Sep;24(9):977-81.
    PMID: 20066730 DOI: 10.1002/bmc.1395
    Capillary zone electrophoresis methods for the simultaneous determination of the beta-blocker drugs, atenolol, chlorthalidone and amiloride, in pharmaceutical formulations have been developed. The influences of several factors (buffer pH, concentration, applied voltage, capillary temperature and injection time) were studied. Using phenobarbital as internal standard, the analytes were all separated in less than 4 min. The separation was carried out in normal polarity mode at 25 degrees C, 25 kV and using hydrodynamic injection (10 s). The separation was effected in an uncoated fused-silica capillary (75 mum i.d. x 52 cm) and a background electrolyte of 25 mm H(3)PO(4) adjusted with 1 m NaOH solution (pH 9.0) and detection at 198 nm. The method was validated with respect to linearity, limit of detection and quantification, accuracy, precision and selectivity. Calibration curves were linear over the range 1-250 microg/mL for atenolol and chlorthalidone and from 2.5-250 microg/mL for amiloride. The relative standard deviations of intra- and inter-day migration times and corrected peak areas were less than 6.0%. The method showed good precision and accuracy and was successfully applied to the simultaneous determination of atenolol, chlorthalidone and amiloride in various pharmaceutical tablets formulations.
    Matched MeSH terms: Molecular Structure
  17. Optimization and validation of RP-HPLC-UV method with solid-phase extraction for determination of buparvaquone in human and rabbit plasma: application to pharmacokinetic study
    Venkatesh G, Majid MI, Ramanathan S, Mansor SM, Nair NK, Croft SL, et al.
    Biomed Chromatogr, 2008 May;22(5):535-41.
    PMID: 18205140 DOI: 10.1002/bmc.965
    A simple, sensitive and specific reversed-phase high-performance liquid chromatographic method with UV detection at 251 nm was developed for quantitation of buparvaquone (BPQ) in human and rabbit plasma. The method utilizes 250 microL of plasma and sample preparation involves protein precipitation followed by solid-phase extraction. The method was validated on a C18 column with mobile phase consisting of ammonium acetate buffer (0.02 m, pH 3.0) and acetonitrile in the ratio of 18:82 (v/v) at a flow rate of 1.1 mL/min. The calibration curves were linear (correlation coefficient>or=0.998) in the selected range. The method is specific and sensitive with limit of quantitation of 50 ng/mL for BPQ. The validated method was found to be accurate and precise in the working calibration range. Stability studies were carried out at different storage conditions and BPQ was found to be stable. Partial validation studies were carried out using rabbit plasma and intra- and inter-day precision and accuracy were within 7%. This method is simple, reliable and can be routinely used for preclinical pharmacokinetic studies for BPQ.
    Matched MeSH terms: Molecular Structure
  18. Synthesis and β-glucuronidase inhibitory activity of 2-arylquinazolin-4(3H)-ones
    Khan KM, Saad SM, Shaikh NN, Hussain S, Fakhri MI, Perveen S, et al.
    Bioorg Med Chem, 2014 Jul 1;22(13):3449-54.
    PMID: 24844756 DOI: 10.1016/j.bmc.2014.04.039
    2-Arylquinazolin-4(3H)-ones 1-25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl2·2H2O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1-25 were evaluated for their β-glucuronidase inhibitory potential. A trend of inhibition IC50 against the enzyme in the range of 0.6-198.2μM, was observed and compared with the standard d-saccharic acid 1,4-lactone (IC50=45.75±2.16μM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC50 values within the range of 0.6-44.0μM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure-activity relationship is established.
    Matched MeSH terms: Molecular Structure
  19. Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities
    Yoon YK, Ali MA, Wei AC, Choon TS, Osman H, Parang K, et al.
    Bioorg Med Chem, 2014 Jan 15;22(2):703-10.
    PMID: 24387981 DOI: 10.1016/j.bmc.2013.12.029
    A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50=58.43μM) as well as for SIRT2 (IC50=45.12μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed.
    Matched MeSH terms: Molecular Structure
  20. Cholinesterase inhibitory activity versus aromatic core multiplicity: a facile green synthesis and molecular docking study of novel piperidone embedded thiazolopyrimidines
    Basiri A, Murugaiyah V, Osman H, Kumar RS, Kia Y, Hooda A, et al.
    Bioorg Med Chem, 2014 Jan 15;22(2):906-16.
    PMID: 24369842 DOI: 10.1016/j.bmc.2013.11.020
    Novel thiazolopyrimidine derivatives have been synthesized via microwave assisted, domino cascade methodology in ionic liquid and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Among the newly synthesized compounds 6d, 6a, 6e and 6b displayed higher AChE inhibitory activity than standard drug, galanthamine, with IC50 values of 0.53, 1.47, 1.62 and 2.05μM, respectively. Interestingly, all the compounds except for 6m-r and 6x displayed higher BChE inhibitory potentials than galanthamine with IC50 values ranging from 1.09 to 18.56μM. Molecular docking simulations for 6d possessing the most potent AChE and BChE inhibitory activities, disclosed its binding interactions at the active site gorge of AChE and BChE enzymes.
    Matched MeSH terms: Molecular Structure
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