Medicinal chemistry (Shāriqah (United Arab Emirates))

Publisher: Bentham Science Publishers

Description

  • Impact factor
    1.64
  • 5-year impact
    0.00
  • Cited half-life
    3.20
  • Immediacy index
    0.27
  • Eigenfactor
    0.00
  • Article influence
    0.00
  • ISSN
    1875-6638

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Bentham Science Publishers

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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of 36 novel substituted quinazolinone derivatives were synthesized and evaluated for their antiinflammatory activity by carrageenan induced paw inflammation model. The ability of these compounds to inhibit cyclooxygenase (COX-1 and 2) enzyme has been determined in-vitro; the results indicated that quinazolinone derivatives were selective towards COX-2 rather than COX-1. Among the quinazolinone derivatives tested, compound 32 showed better inhibition against COX-2 when compared with Celecoxib. Pharmacophore modeling and 3D QSAR studies were performed in order to elucidate structural insights for the anti-inflammatory activity.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 10/2014; 10(7):711-723.
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    ABSTRACT: Ever growing resistance by the pathogenic bacteria against the prevalent antibiotics has forced the researchers to look for new methods and techniques to design effective antimicrobial agents. In the present study a new tetracycline-based antimicrobial polymer (AMP) was synthesized via acryloylation method using lipase-catalyzed esterification of tetracycline with methacrylic acid (MAAc). The aforesaid polymer was transformed into nanoparticles by an emulsion method. These polymers were characterized by various techniques, i.e., FTIR, NMR, XRD, SEM, and EDAX. The antibacterial activity of the AMPs was studied against two bacteria P. aeruginosa [resistant (-)] and S. aureus [susceptible (+)]. The synthesized AMP was observed to be more potent and efficient antimicrobial agent than the precursor tetracycline.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 05/2014;
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    ABSTRACT: A series of twelve analogs carrying fluoro, chloro, bromo and iodo halogens on the ortho, meta and para positions of a benzoyloxytropane skeleton were synthesized by a simple acylation of 8-methyl-8-aza-bicyclo[3.2.1]octan-3α-ol by halogenobenzoyl chlorides. The compounds were evaluated in vitro against Plasmodium falciparum (P. f.), Trypanosoma brucei brucei (T. b. b.), Trypanosoma cruzi (T. c.) and Leishmania infantum (L. i.). This study shows that the presence of a halogenated atom and its position on the aromatic ring are important for in vitro activity. Compounds 4 (IC50 = 3.6 µM), 8 (IC50 = 6.7 µM), 5 (IC50 = 8.1 µM) and 7 (IC50 = 9.5 µM) were found the most active against P. f., whereas compounds 12 (IC50 = 5.1 µM), 11 (IC50 = 5.6 µM) and 9 (IC50 = 5.8 µM) exhibited the most pronounced activity against T. b. b. This series of compounds can be considered as non-toxic to the human cell line MRC-5.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 05/2014;
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    ABSTRACT: Valproic acid (VPA) is considered first-line treatment for primarily generalized idiopathic seizures such as absence, generalized tonic-clonic and myoclonic seizures. Among major antiepileptic drugs, VPA is also considered effective in childhood epilepsies and infantile spasms. Due to its broad activity, it acts as a mood stabilizer in bipolar disorder and it is useful in migraine prophylaxis. Despite its long-standing usage, severe reactions to VPA, such as liver toxicity and teratogenicity, are reported. To circumvent side effects due to structural characteristics of VPA, a new VPA-aminoacid conjugate, the N-valproyl-L-Phenylalanine, has been synthesized in good yield and characterized by FT-IR, MS, 13C and 1H- NMR analyses. The Log DpH7.4 (0.19) indicate that this new molecule potentially is able to cross biological membranes. The resistence to chemical and enzymatic hydrolysis of N-valproyl-L-Phenylalanine were also assessed. All trials suggested that the compound at the pH conditions of the entire gastro-intestinal tract remained unmodified. Moreover, the novel compound did not undergo enzymatic cleavage both in plasma and in cerebral medium up to 24 h. Toxicity assay on primary cultures of astrocytes indicated that synthetized conjugate is less toxic than both free VPA and L-Phenylalanine. In this paper, the anticonvulsant activity of the new compound against epileptic burst discharges evoked in vitro in rat hippocampal slices was also evaluated. These preliminary results underlines that N-valproyl-L-Phenylalanine could represent a good candidate to further investigation as new potential antiepileptic agent.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 05/2014;
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    ABSTRACT: Background: Cholesterol is essential for the growth and maintenance of mammalian cells. However, elevated level of serum cholesterol is among the associated risk factors for the coronary heart disease. Cholesterol is derived from two different sources of endogenous synthesis and diet. Statins can reduce endogenous sterol synthesis by inhibit HMG-CoA reductase, whereas cholesterol absorption inhibitors, such as ezetimibe, can block cholesterol uptake from dietary sources by block Niemann-Pick C1-like 1 (NPC1L1). Objective: The present review focus on the main research progress of cholesterol absorption inhibitors, the structure of NPC1L1 and discovery of novel chemical entities by virtual screening. Conclusion: Studies on the structure-activity relationship reveal that azetidinone is important to keep activity in azetidinone derivatives and the novel heterocyclic compounds with replacement of β-lactam scaffold by oxazolidinone also shows similar activity as ezetimibe. Virtual screening in data bases as computer-aided molecular design tools to propose novel cholesterol absorption inhibitors are kind of complement to design and synthesize structurally novel compounds.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 04/2014;
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    ABSTRACT: Estrogen receptors (ERs) are members of a superfamily of ligand-modulated nuclear receptors, which have been associated with an increased risk of cardiovascular diseases and breast cancer. Based on molecular docking studies, 1,4-dihydrothieno[3',2':5,6]thiopyrano[4,3-c]pyrazole-3-carboxamide derivatives as estrogen receptor inhibitors with a new scaffold , have been synthesized and tested for the antitumor activity on the ER expressing (ER dependent) human MCF-7 breast cancer cell line. According to the biological activity evaluation, compound 6a demonstrated the most potent antiproliferative activity (relative inhibitory rate: 100%). Several of these compounds exhibited moderate antitumor activity and worthy of further modification to obtain more potent anticancer candidate drugs.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 04/2014;
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    ABSTRACT: Derivatives of quinoxalinedione (QX) were chosen as chemical lead for the development of new radioligands for the AMPA receptor, since there are several examples of QX-derivatives with high affinity. The radiosyntheses of the new compounds 6-[18F]fluoro-7-nitro-QX ([18F]FNQX) and 6-[18F]fluoro-7-cyano-QX ([18F]FCQX) with radiochemical yields of 8 ± 2 and 3 ± 2 %, respectively, as well as the evaluation of their binding properties to the AMPA-receptor were performed. A comparison of the Ki-values of the new QX-derivatives FCQX and FNQX with mono-substituted cyano- and nitro-QX shows negligibly small differences of affinity (within the range of 1.4 to 5 µM), but exhibits a tenfold lower affinity than derivatives with two electron withdrawing groups like the 7-cyano-6-nitro-compound CNQX and the 6,7-dinitro compound DNQX. Thus, with respect to the low affinity and a high non-specific binding with in vitro and ex vivo autoradiographic studies, the new compounds do not lend themselves for in vivo imaging.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 04/2014;
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    ABSTRACT: We have synthesized a series of anthrapyrazoles derivatives. The biological results indicated that these derivatives exhibited potent in vitro cytotoxicity against different cancer cell lines (human hepatocellular carcinoma HepG2 and BEL-7402, human colonic carcinoma HCT-116 and HT-29) and drug-resistant human hepatoma cell line (SMMC-7721). Among them, the polyamine-based anthrapyrazole derivatives 4c and 4f-g showed superior cytotoxicity than that of Mitoxantrone both on cancer cell lines and the drug-resistant subline. However, the DNA relaxation assay revealed that they had insignificant topoisomerase II inhibition. These results clearly indicate that polyamine side chains will have a profound effect on the cytotoxicity of anthrapyrazoles derivatives.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 04/2014;
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    ABSTRACT: Electronic-Topological Method application and a variant of Feed Forward Neural Network (FFNN) identified as the Associative Neural Network to the compounds Hydrazones derivatives has been used to develop a prediction system of antituberculosis activity. The supervised learning has been performed using (ASNN) and categorized correctly 84.4%, or 38 compounds from 45. Ph1 pharmacophore consisting of 6 atoms and Ph2 pharmacophore consisting of 7 atoms were found. Anti-pharmacophore features being break of activity have also been revealed and APh1 found in 22 inactive molecules. Statistical analyses have been carried out by using the descriptors, such as EHOMO, ELUMO, ΔE, hardness, softness, chemical potential, electrophilicity index, exact polarizibility, total of electronic and zero point energies, dipole moment as independent variable in order to account for the dependent variable called inhibition efficiency. That observing several complexities, namely, linearity, nonlinearity and multi-co linearity at the same time leads data to be modeled using two different techniques called multiple regression and Artificial Neural Networks (ANNs) after computing correlations among descriptors in order to compute QSAR. Computations resulting in determination of some compounds with relatively high values of inhibition are presented.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 04/2014;
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    ABSTRACT: This paper describes preparation and in vitro evaluation of 19 compounds related to the selective experimental cholinesterase inhibitor BW284c51. The novel compounds were prepared as fragments of parent molecule BW284c51 and evaluated on the model of human recombinant acetylcholinesterase and human plasmatic butyrylcholinesterase. The IC50 values of the prepared compounds were compared to the parent molecule BW284c51. None of the compounds was superior to the parent drug, but two BW284c51 fragments showed promising hAChE inhibition in µM scale and improved selectivity. These two fragments were further subjected to the molecular modelling study and their enzyme interactions were rationalized. The structure-activity relationship of the prepared series was stated.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 04/2014;
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    ABSTRACT: In this study, 12 new oxime ether derivatives, which were expected to show anticonvulsant and antimicrobial activities, were synthesized. Oxime ether derivatives were synthesized by the reaction of various alkyl halides with 1-(2-naphthyl)-2-(pyrazol-1-yl)ethanone oxime. Anticonvulsant activity of the compounds was determined by maximal electroshock (MES) and subcutaneous metrazol (ScM) seizure tests, while neurological disorders were evaluated using rotorod toxicity test according to the ASP of NIH. Compound 1, 6 and 7 showed anticonvulsant activity at 300 mg/kg dose at 4 h, but compounds 1 and 7 showed toxicity at 300 mg/kg dose at half an hour. Antimicrobial activities of the compounds were also determined using agar microdilution method. Compound 1 and 5 were found to have the highest antifungal activity among the other compounds.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 04/2014;
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    ABSTRACT: Selective uncompetitive antagonists of the phencyclidine (PCP) binding site of the N-methyl-D-aspartate receptor (NMDAR) are known to have therapeutic potential as anticonvulsants and neuroprotective agents. Several fluorinated molecules with each containing a cycloheptane ring were designed to probe the PCP pharmacophore and test the influence of fluorine substitution on NMDAR binding and in vivo efficacy. Syntheses and analyses of six novel compounds, 1-(4-fluorophenyl)cycloheptanamine (3), 1-(1-(4-fluorophenyl)cycloheptyl)piperidine (4), 1-(1-(4-fluorophenyl)cycloheptyl)pyrrolidine (5), 1-(3-fluorophenyl)cycloheptanamine (6), 1-(1-(3-fluorophenyl)cycloheptyl)piperidine (7), 1-(1-(3-fluorophenyl)cycloheptyl)pyrrolidine (8) and several related reference arylcyloalkylamines are described. Receptor binding was performed at the PCP site of NMDAR for each compound using [3H]-(+)-MK-801 displacement. Unexpectedly, the 3-fluoro- primary amine 6 had the greatest affinity of the series and these binding results support a different structure activity relationship (SAR) profile for arylcycloheptylamines when compared to arylcyclohexylamines like PCP. Five of the novel compounds have affinity (Ki) in the hundred nM (10-7) range. In addition, compounds 3, 5, 6, 7 and 8 were evaluated and found to exhibit neuroprotective effects from NMDA induced toxicity in vitro and compounds 6, 7 and 8 exhibited anticonvulsant activities in rats. An ED50 of 13.84 mg/kg was found for compound 6 in rat MES test with a protective index (PI) of 3.66 against ataxia. These results support further investigation of the arylcycloheptylamine class.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 04/2014;
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    ABSTRACT: Only 10% of all compounds developed by pharmaceutical companies make it to the market. Of the 90% that do not make it to the market, 50% either have toxicity or pharmacokinetic issues. Thus, the need for ADMET (absorption, distribution, metabolism, excretion and toxicity) optimization during the early stages of drug development is clear. In silico tools may be promising for this use due to their lower cost and time requirements. This review aims to evaluate the predictive power of intestinal absorption and oral bioavailability prediction methods using different statistical approaches over time. Improvement, refinement and diversification of these methods have been observed over the past few years. Nevertheless, some elements related to the quality of the biological data, disclosure of the data used and description of validation methods, that could contribute to building new, better and more reliable models have been ignored by researchers or restricted by the technical limitations of various laboratories.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 04/2014;
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    ABSTRACT: This manuscript describes the protein anti-glycation activity of thirty-three (33) benzothiazoles, out of which twenty-seven were newly synthesized benzothiazoles. Compound 1 (IC50= 187 ± 2.6 µM) was found to be the most active, while compounds 2 (IC50= 219 ± 3.6 µM), 3 (IC50= 224 ± 1.9 µM), 4 (IC50= 223 ± 3.3 µM), 5 (IC50= 238 ± 2.2 µM), 7 (IC50= 266 ± 5.4 µM), 17 (IC50= 226 ± 1.6 µM) and 18 (IC50= 274 ± 3.6 µM) were significantly active, when compared with the standard rutin (IC50= 294 ± 1.5 µM). This study identified potential inhibitors of methylglyoxal mediated glycation of proteins.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 03/2014;
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    ABSTRACT: A series of 2´-hydroxy-4´-isoprenyloxychalcone derivatives were synthesized and evaluated their antidepr- essant-like activity using the FST and TST. All compounds exhibited the potential antidepressant-like activity in the FST and the TST through intraperitoneal (ip) injection. Among them, compounds 4i, 4l and 4n exhibited more potent antidepressant-like activity at a dose of 10 mg/kg. And, compounds 4i, 4l and 4n were also adequately absorbed in mice after oral administration at a dose of 30 mg/kg. In the 5-HT induced head-twitch test and yohimbine induced mortality test, compound 4i could increase the head-twitch and rise mortality mice. The results suggested that the antidepressant effects of compound 4i may be related to via the serotonergic and noradrenergic system.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 03/2014;
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    ABSTRACT: The synthesis and chemical characterization of the novel 2,6-diacetylpyridine-bis(selenosemicarbazone) metal complexes of Zn(II), Cd(II) and Ni(II) was published previously. Here we report first evidence on anti-proliferative activity of the complexes and molecular patterns that underlie it. The complexes and the corresponding ligand are shown to be cytotoxic on the panel of nine, malignant and non-malignant cell lines, with the exception of Ni(II) complex that did not achieve IC50 value on any of the cell lines tested. Further experiments on the selected cell lines including A 549, MRC-5, EA.hy 926 and HeLa, have shown that the complexes posses unambiguous property of inducing necrosis in the cells treated for 6 hours, with the ligand and Zn(II) complex being the most active on all cell lines. On the contrary, only small portion of early apoptotic events was detected, under the same experimental condition. This was in complete concordance with the results obtained from Western blot analysis of the treated cells that showed no or slight increase of the protein amounts of two crucial apoptotic mediators: Cytochrome C and Caspase III. We propose the model, under which tested complexes induce necroptosis in treated cells, a recently described type of cell death with necrotic morphological features and acting via caspase independent pathway, and without elevated amounts of intracellular ROS. Endothelial EA.hy 926 cells have proven to be extremely sensitive on the necrosis-inducing effect of the complexes, which could indicate potential anti-angiogenic effect of the novel complexes that is to be investigated.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 03/2014;
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    ABSTRACT: To explore apolipoprotein E gene variants distribution among the patients of Alzheimer's disease and vascular dementia for the elderly community population in Nanking, the polymerase chain reaction and restriction fragment length polymorphism techniques were employed to analyze the gene frequency of apolipoprotein E (ApoE) for 113 cases with Alzheimer's disease (AD), 85 cases with vascular dementia (VaD), 147 cases with questionable dementia (QD), and 396 dementia-free controls. It was found that ApoE ε4 gene container (37.17%) and allele frequency (21.24±2.72) of ApoE ε4 in AD group were significantly higher than those in both control and VaD group (p<0.05). With the increment of ε4 gene dose, the incidence of the AD was significantly increased. Compared with the control group, ApoE ε4 had risk ratio (RR) of 1.82 to develop AD (p =4e-4), and attributable risk percentage (ARP) of 45%. These results suggest that ApoE ε4 gene may be responsible for up to 45% of the genetic component of Alzheimer's disease, and may act as a discriminator between AD and VaD as well.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 03/2014;
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    ABSTRACT: Twenty-three (23) derivatives of coumarin (5-27) were synthesized and screened for their in vitro β-glucuronidase (E. coli) inhibitory activities. Only three compounds, 7,8-dihydroxy-4-methyl-2H-chromen-2-one (9) (IC50 = 52.39 ± 1.85 μM), 3-chloro-6-hexyl-7-hydroxy-4-methyl-2H-chromen-2-one (18) (IC50 = 60.50 ± 0.87 μM), and 3,6-dichloro-7-hydroxy-4-methyl-2H-chromen-2-one (15) (IC50 = 380.26 ± 0.92 μM) displayed activities against β-glucuronidase as compared to standard D-saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 µM). The results indicated that the activity of the synthetic coumarins dependent upon the substituents present on the coumarin skeleton.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 03/2014;