Hasrat Ali

Université de Sherbrooke, Sherbrooke, Quebec, Canada

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Publications (97)220.96 Total impact

  • Hasrat Ali, Johan E. van Lier
    Tetrahedron Letters 07/2014; 55(30):4163–4167. · 2.40 Impact Factor
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    ABSTRACT: The synthesis of a series of new fluorinated phthalocyanines and porphyrins as potential bimodal probes is evaluated. In these complexes, zinc phthalocyanine functions as a fluorescence imaging moiety while attachment of an aliphatic chain of different lengths bearing a tosylate group permits introduction of fluorine via nucleophilic substitution of the tosylate group. Using short-lived [18F]fluoride gives the analogous 18F-radiolabelled tracer rendering the bimodal probe suitable for both fluorescence and PET imaging.
    Journal of Porphyrins and Phthalocyanines 08/2013; 17(08n09). · 1.43 Impact Factor
  • Hasrat Ali, Johan E. van Lier
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    ABSTRACT: Rhodium-catalyzed carbon–carbon bond forming reactions using phthalocyanine-boronate ester were investigated. The reaction of Pc-boronate ester with substituted aldehydes gave 1,2-addition products (secondary alcohols), while α,β-unsaturated carbonyl compounds (aldehydes, ketones, esters, and amides) furnished 1,4-addition products. The reaction of Pc-substituted alkynes with o-formyl and acetyl phenylboronic acid gave 1H- and 1-methyl inden-1-ol annulation derivatives. All reactions were performed in mixtures of organic–aqueous solvents.
    Tetrahedron Letters 06/2013; 54(23):2956–2959. · 2.40 Impact Factor
  • Hasrat Ali, Johan E. van Lier
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    ABSTRACT: An easy synthetic method for the preparation of pyrazine-2,3-dicarbonitrile 5,6-bis-substituted derivatives using Pd-catalyzed cross coupling reaction (Sonogashira, Suzuki, Heck) is described. The reaction conditions allow preparing symmetrical and unsymmetrical bis-substituted products in moderate to high yields, as precursors for the preparation of highly substituted symmetrical and non-symmetrical aza-phthalocyanines with well-defined spectral properties.
    Tetrahedron Letters 09/2012; 53(36):4824–4827. · 2.40 Impact Factor
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    ABSTRACT: Sulfonated metallo phthalocyanines (MPcS(n)) are second generation photosensitizers advanced for photodynamic therapy of various medical applications. A series of ZnPcS(n) was demetallated and subsequently converted to the corresponding [(64)Cu]CuPcS(n) in 40-50% isolated yields and >98% radiochemical purities. Tumor-bearing mice were injected with the (64)Cu-labeled products and subjected to 3-h dynamic PET imaging studies. Biodistribution patterns showed characteristic differences between the various derivatives. Tumor uptake was detected only for the amphiphilic derivatives [(64)Cu]CuPcS(2) and [(64)Cu]CuPcS(3)C(6) (1-1.5%ID/g). The biological data suggest that PET imaging with [(64)Cu]CuPc can be used to establish structure-PDT efficacy relationships for Pc-based photosensitizers.
    Bioorganic & medicinal chemistry letters 10/2011; 21(24):7470-3. · 2.65 Impact Factor
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    ABSTRACT: Phthalocyanines (Pc) were conjugated with peptide moieties to improve their target selectivity for potential use as fluorescence and/or positron emission tomography (PET) probes in medical imaging. Three synthetic methods based on palladium-catalyzed cross-coupling reactions (Sonogashira, Buchwald-Hartwig, and Suzuki-Miyaura) were investigated. Using these methods, a series of peptides monofunctionalized with Pc at the N/C-terminal position or on a phenylalanine side chain was obtained in good yields and characterized.
    The Journal of Organic Chemistry 02/2011; 76(6):1887-90. · 4.56 Impact Factor
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    ABSTRACT: Palladium-catalyzed copper-free Sonogashira cross-coupling reactions were performed on a protected and unprotected monoiodotriglycerol substituted Zn(II) phthalocyanine with various alkynes in organic and aqueous medium. From the silyl protected alkyne derivative, a protected homo coupled dimeric product was also prepared using Glaser coupling. All products were purified by reverse phase HPLC and the assigned structures were confirmed by mass and UV–vis spectroscopy.
    Tetrahedron Letters - TETRAHEDRON LETT. 01/2011; 52(34):4395-4397.
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    ABSTRACT: The impact of lipophilicity on biological parameters critical to photodynamic efficacy was analyzed for a new generation of trisulfobenzo(mononaphtho)porphyrazines. The porphyrazines were substituted on the naphtho ring with linear alkynyl side chains of various lengths. When compared to the analogous phthalocyanine structures, the added benzo ring in the porphyrazine structures increased the lipophilicity for analogs with short alkynyl chains, while this effect disappeared for analogs with longer side chains. In aqueous media, the analogous phthalocyanine series showed aggregation tendencies. In contrast, no correlation between aggregate formation and the length of the alkynyl side chain was evident in the porphyrazine series. At low concentrations, the length of the side chain did not affect cell uptake, while phototoxicity towards EMT-6 mouse tumour cells showed a parabolic relationship, where the hexynyl derivative showed the highest activity. The trisulfonated porphyrazines localized at intracellular organelles, plasma and perinuclear membranes, but could not be found in the nucleus. Total cell uptake of dye did not correlate with phototoxicity, suggesting that localization in certain intracellular organelles, and distribution into critical intracellular sites are important determinants of their photodynamic activity. The hexynyl trisulfonated zinc porphyrazine derivative (ZnNPcS(3)C(6)) showed the strongest in vitro photodynamic activity and therefore was further studied in an EMT-6 mouse tumour model. An i.v. dose of 1 micromol of ZnNPS(3)C(6) per kg, followed 24 h later by activation with light, induced 100% tumour necrosis within 24 h post-PDT. This treatment delayed tumour volume doubling time from 5 days to >2 weeks, and gave 41% tumour cure >3 weeks post-PDT. Applying the same light dose fractionated (5 min on, 2 min off), further improved tumour response, leading to a doubling time of 26 days and a 73% tumour cure. At the administered 1 micromol kg(-1) dye dose, no skin phototoxicity was observed and >90% blood clearance was observed within 5 h post-injection. Compared to the analogous trisulfo monohexynyl zinc phthalocyanine, the new trisulfobenzo(mononaphthohexynyl)porphyrazine provided a broader range of excitation wavelengths, and improved photodynamic potency, while apparently being free of unwanted systemic side effects.
    Photochemical and Photobiological Sciences 03/2010; 9(3):331-41. · 2.92 Impact Factor
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 33(30).
  • [Show abstract] [Hide abstract]
    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 30(51).
  • H. ALI, J. E. VAN LIER
    [Show abstract] [Hide abstract]
    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 28(23).
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    ABSTRACT: A new series of water-soluble, mononaphthotrisulfobenzoporphyrazines, bearing an alkynyl side chain of varying lengths on the naphtho ring, were prepared and tested for their efficacy to inhibit plasma extravasation when used as photosensitizers during photodynamic therapy (PDT) of the retina in the rat. The hexynyl substituted photosensitizer was the most potent, and was able to produce complete inhibition, at low doses of photosensitizer and light.
    Journal of Medicinal Chemistry 07/2009; 52(14):4107-10. · 5.61 Impact Factor
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    ABSTRACT: Tetrasulfonated zinc phthalocyanine (ZnPcS(4)) is a potent sensitizer for photodynamic therapy of various medical conditions. Depending on its mode of preparation the material consists of mixtures of ortho and meta sulfonated derivatives as well as regioisomers with different photodynamic potency. To study the effect of the site of substitution on biological parameters that contribute to overall photodynamic efficacy, a series of pure ortho- and meta-tetravinylsulfonated metallo phthalocyanines MPc-o/m-(VS)(4) were prepared from the corresponding tetraiodo phthalocyanines using the palladium-catalyzed cross-coupling reaction (Heck reaction). Compared to the tetrasulfonated phthalocyanines, the tetravinylsulfonated derivatives are more hydrophobic and their Q-band absorption maxima are red-shifted. While their in vitro phototoxicity is in the same range as the mixed isomeric sulfonated derivatives, ortho-substituted MPc-o-(VS)(4) are more photocytotoxic as compared to their corresponding meta analogs. Although the central metal ion and site of substitution affect aggregation, the tendency to aggregate did not correlate with photodynamic potency nor did overall cell uptake. Instead, intracellular localization at both mitochondrial and lysosomal membranes appears to be the major factor explaining the augmented activity of the ortho substituted derivatives.
    Photochemical and Photobiological Sciences 07/2009; 8(6):868-74. · 2.92 Impact Factor
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    ABSTRACT: With the aim to develop improved dual-action sensitizers suitable for both photodynamic therapy (PDT) and radiotherapy, we prepared a series of metal and metal-free cationic porphyrins, brominated either on beta- or N-allyl positions. Photo- and radiosensitizing efficacy was evaluated in MDA-MB-231 breast cancer cells incubated with 1 muM porphyrin and treated with graded doses of visible light or 0-6 Gy of 60Co gamma irradiation. Metabolic activity after PDT or cell survival after gamma irradiation were estimated by a colorimetric (MTT) or clonogenicity assay, respectively. The highest photo- and radiosensitizing activities were observed with the porphyrins substituted with bromines on N-allyl positions. The non-metalated N-allyl bromoporphyrin exhibited the highest photocytotoxicity (LD50=4.1+/-0.6 J cm(-2), compared to 15.3+/-2.2 J cm(-2) for the non-brominated analog). The radiosensitizing capacity of the cationic porphyrins was also affected by these substitutions with the non-metalated N-allyl bromo analog showing the best improvement (LD50=1.2+/-0.4 Gy vs. 3.6+/-0.9 Gy for the non-brominated analog). The increased photodynamic and radiosensitizing potencies due to bromine addition hold potential for the development of new, improved drugs for cancer treatment in combination with photodynamic and radiation therapy.
    Photochemical and Photobiological Sciences 03/2009; 8(2):224-32. · 2.92 Impact Factor
  • Hasrat Ali, Johan E. van Lier
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    ABSTRACT: An efficient one-step method for the synthesis of covalently linked phthalocyanine–porphyrin (Pc–Por) hetero-dyads and Pc–Por–Pc hetero-triads, connected directly through C–C bonds, is presented. The procedure utilizes a Pd-mediated Suzuki cross-coupling reaction of a Pc–boronate synthon and a halogenated porphyrin. The two chromophores are directly linked, without spacer, through the β-pyrrolic-, meso-, and para-position of the meso-phenyl group of the porphyrins. The electronic absorption spectrum of the Pc–Por–Pc triad shows red-shifted, split Q-bands reflecting energy transfer.
    Tetrahedron Letters - TETRAHEDRON LETT. 01/2009; 50(10):1113-1116.
  • Source
    Hasrat Ali, Johan E. van Lier
    [Show abstract] [Hide abstract]
    ABSTRACT: Covalently linked phthalocyanine–phthalocyanine (Pc–Pc) heterodimers and Pc–Pc triad phthalocyanines connected through phenyl–phenyl (C–C) linkages are prepared using phthalocyanine-boronate (Suzuki Pc-synthon) and palladium catalyst.
    Tetrahedron Letters - TETRAHEDRON LETT. 01/2009; 50(3):337-339.
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    ABSTRACT: Covalently C–C linked Pc–Pc homo-dimers (ortho and meta) were synthesized from their corresponding Pc halide precursors using a Pd-catalyzed homo-coupling reaction. Photophysical data reveal energy transfer between the Pc moieties resulting in the appearance of new red-shift Q-bands that correlate to the planarity and dihedral angle between the subunit.
    Tetrahedron Letters 12/2008; 49(51):7253. · 2.40 Impact Factor
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    ABSTRACT: The 2-methoxy derivative of estradiol is currently in Phase II clinical trial as an anticancer agent while the 4-methyl derivative has been shown to interact with cytoplasmic and nuclear estrogen receptors in rat pituitary gland and hypothalamus. We hypothesize that the 16alpha-(18)F-analogs of these estrogens could be suitable radiotracers to evaluate action mechanisms of the parent compounds. In this study we report the synthesis of the 16alpha-(18)F and 16alpha-(19)F-analogs of the A-ring substituted estradiols in high yield via stereoselective opening of the intermediate 16beta,17beta-O-cyclic sulfones with [(18)F]F(-) or F(-) followed by deprotection.
    Steroids 10/2008; 74(1):42-50. · 2.80 Impact Factor
  • Journal of Porphyrins and Phthalocyanines - J PORPHYR PHTHALOCYA. 01/2007; 11(08).
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    ABSTRACT: The formation of secondary products during the radioiodination of aromatic amines is reported. Iodination of a series of N,N-dimethyl-N'-(alkylphenyl)-1,3-propanediamines with IC1 in the presence of AcOH and HClO4 gave in addition to the expected iodo derivatives substantially amounts of secondary cleavage products which were identified as the corresponding iodobenzaldehyde derivatives.
    Journal of Labelled Compounds 07/2006; 27(1):117 - 122.

Publication Stats

985 Citations
220.96 Total Impact Points

Institutions

  • 1985–2014
    • Université de Sherbrooke
      • • Department of Nuclear Medicine and Radiobiology
      • • Department of Medicine
      Sherbrooke, Quebec, Canada
  • 1999–2000
    • Université du Québec
      Québec, Quebec, Canada
  • 1993
    • Soreq Nuclear Research Center
      Yerushalayim, Jerusalem District, Israel
  • 1992
    • University of Padova
      • Department of Biology
      Padova, Veneto, Italy