Hang Zhang

Peking University Health Science Center, Peping, Beijing, China

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Publications (6)15.83 Total impact

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    ABSTRACT: A series of novel HIV-1 protease inhibitors based on the (hydroxyethylamino)-sulfonamide isostere incorporating substituted phenyls and benzheterocycle derivatives bearing rich hydrogen bonding acceptors as P(2) ligands were synthesized. Prolonged chain linking the benzhereocycle to the carbonyl group resulted in partial loss of binding affinities. Introduction of a small alkyl substituent with appropriate size to the -CH2- of P(1)-P(2) linkage as a side chain resulted in improved inhibitory potency, and in this study, isopropyl was the best side chain. Replacement of the isobutyl substituent at P(1)'group with phenyl substituent decreased the inhibitory potency. One of the most potent inhibitor, compound 23 showing high affinity to HIV-1 protease with an IC(50) value of 5 nM, also exhibited good anti-SIV activity (EC(50) = 0.8 microM) with low toxicity (TC(50) > 100 microM). The flexible docking of inhibitor 23 to HIV-1 protease active site rationalized the interactions with protease.
    Full-text · Article · Aug 2010 · Chemical Biology & Drug Design
  • Meizi He · Hang Zhang · Xiaomin Deng · Ming Yang

    No preview · Article · Oct 2008 · Journal of Biotechnology
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    ABSTRACT: Two new Co(II) and Ni(II) complexes exhibiting DNA cytotoxic activities with 3-(2-pyridyl)pyrazole-based ligand, [Co(L)(3)](ClO(4))(2) (1) and [Ni(L)(3)](ClO(4))(2) (2) (L=1-[3-(2-pyridyl)-pyrazol-1-ylmethyl]-naphthalene) were synthesized and structurally characterized. Both 1 and 2 crystallized in the monoclinic system, space group P2(1)/c, for 1, a=12.8324(8), b=12.1205(8), c=33.27(2) A, beta=93.92(3) degrees and Z=4; for 2, a=12.8764(3), b=12.1015(3), c=33.2415(9) A, beta=93.998(1) degrees and Z=4. Among them, the Co(II) and Ni(II) ions were all coordinated by six N donors from three distinct L ligands. In addition, the cytotoxic activities of 1, 2 and L in vitro were evaluated against three different cancer cell lines HL-60 (human leukemia), BGC-823 (stomach cancer) and MDA-MB-435 (mammary cancer), respectively. The results showed that 1 exhibited significantly high cytotoxic activities against HL-60 and moderate activities against BGC-823 and MDA-MB-435. In order to further investigate the relationships between structures and DNA-binding behaviors of these complexes, the interactions of 1, 2 and L with calf thymus DNA (CT-DNA) were then subjected to thermal denaturation, viscosity measurements and spectrophotometric methods. The results indicated that 1 and 2 intercalated with DNA via L ligand. The intrinsic binding constants of 1, 2 and L with DNA were 1.6x10(4), 5.6x10(3) and 2.76x10(3) M(-1), respectively.
    No preview · Article · Aug 2007 · CHEMICAL & PHARMACEUTICAL BULLETIN
  • Ran Chen · Chun-Sen Liu · Hang Zhang · Yue Guo · Xian-He Bu · Ming Yang
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    ABSTRACT: Three new complexes [Cu(L)(2)(NO(3))](NO(3))(H(2)O)(1/2)(CH(3)OH)(1/2) (1), [Cd(L)(2)(NO(3))(2)](H(2)O)(3) (2) and [Cd(L)(2)(ClO(4))(CH(3)OH)](ClO(4))(H(2)O)(1/4)(CH(3)OH) (3) (L=1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene) were synthesized and characterized by elemental analyses, IR and X-ray diffraction analysis. Among them, the Cu(II) and Cd(II) ions were both coordinated by four N donors from two distinct L ligands via N,N-bidentate chelating coordination mode. Additional weak interactions, such as the face-to-face pi-pi stacking and C-Hcdots, three dots, centeredO H-bonding interactions, linked the mononuclear unit into 1D chain and further into 2D network. Complexes 1-3 were subjected to biological assays in vitro against six different cancer cell lines. All of them exhibited cytotoxic specificity and notable cancer cell inhibitory rate. The interactions of 1-3 with calf thymus DNA were investigated by thermal denaturation, viscosity measurements, spectrophotometric and electrophoresis methods. The results indicate that these complexes bound to DNA by intercalation mode via the ligand L and had different nuclease activities, which were in good agreement with their DNA-binding strength. Moreover, the central metal ions of 1-3 played a vital role in DNA-binding behaviors, DNA-cleavage activities and cytotoxicities, whereas the contribution of the different counter anions to their bioactivities also should not be ignored.
    No preview · Article · Apr 2007 · Journal of Inorganic Biochemistry
  • Chun-Lai Sun · Rui-Fang Pang · Hang Zhang · Ming Yang
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    ABSTRACT: Twenty-four 4-hydroxypyrone derivatives were synthesized with a facile synthetic method to develop novel HIV protease inhibitors. Most of them were shown to display good antiviral activities in SIV-infected CEM cells. The introduction of alpha-naphthylmethyl group to C-6 of 5,6-dihydropyran-2-ones led to an effective antiviral compound that showed an EC(50) value at 1.7 microM with a therapeutic index of 46.
    No preview · Article · Aug 2005 · Bioorganic & Medicinal Chemistry Letters
  • Hang Zhang · Chun-Sen Liu · Xian-He Bu · Ming Yang
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    ABSTRACT: A new ligand L, 1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene, and its two metal complexes, [Cu(L)3](ClO4)2 (1) and [Zn(L)3](ClO4)2(H2O)2 (2), have been synthesized and characterized. The crystal structure of complex 1 was determined by single crystal X-ray diffraction, which crystallized in monoclinic, space group P2(1)/n with unit cell parameters, a = 12.710(4) angstroms, b = 12.135(3) angstroms, c = 33.450(9) angstroms, beta = 93.281(5) degrees and Z = 4. The Cu atom was six-coordinated to N(1), N(2), N(4), N(5), N(7) and N(8) from three L ligands and formed a slightly distorted octahedral geometry. Complexes 1 and 2, and ligand L were subjected to biological tests in vitro using three different cancer cell lines (HL-60, BGC-823 and MDA-MB-435). Complex 1 showed significant cytotoxic activity against three cancer cell lines. The interactions of complexes 1 and 2, and ligand L with calf thymus DNA were then investigated by thermal denaturation, viscosity measurements and spectrophotometric methods. The experimental results indicated that complexes 1 and 2 bound to DNA by intercalative mode via the ligand L. The intrinsic binding constants of complexes 1 and 2, and ligand L with DNA were 1.8 x 10(4), 5.4 x 10(3) and 2.76 x 10(3) M(-1), respectively.
    No preview · Article · Jun 2005 · Journal of Inorganic Biochemistry