Bioreductively Activatable Prodrug Conjugates of Combretastatin A-1 and Combretastatin A-4 as Anticancer Agents Targeted toward Tumor-Associated Hypoxia
Winn, Blake A.; Devkota, Laxman; Kuch, Bunnarack; MacDonough, Matthew T.; Strecker, Tracy E.; Wang, Yifan; Shi, Zhe; Gerberich, Jeni L.; Mondal, Deboprosad; Ramirez, Alejandro J.; Hamel, Ernest; Chaplin, David J.; Davis, Peter; Mason, Ralph P.; Trawick, Mary Lynn; Pinney, Kevin G.; Journal of Natural Products  (2020) –; doi:10.1021/acs.jnatprod.9b00773

data_1557632
_publ_section_title
;
 Bioreductively Activatable Prodrug Conjugates of Combretastatin A-1 and
 Combretastatin A-4 as Anticancer Agents Targeted toward Tumor-Associated
 Hypoxia
;
_journal_name_full               'Journal of Natural Products'
_journal_paper_doi               10.1021/acs.jnatprod.9b00773
_journal_year                    2020
_chemical_formula_sum            'C25 H27 N O7 S'
_chemical_formula_weight         485.53
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   geom
_audit_creation_method           SHELXL-2014
_cell_angle_alpha                100.514(5)
_cell_angle_beta                 104.240(5)
_cell_angle_gamma                108.180(5)
_cell_formula_units_Z            2
_cell_length_a                   8.0895(7)
_cell_length_b                   12.0696(10)
_cell_length_c                   14.0112(12)
_cell_measurement_reflns_used    3182
_cell_measurement_temperature    110(2)
_cell_measurement_theta_max      23.51
_cell_measurement_theta_min      2.74
_cell_volume                     1208.85(19)
_computing_cell_refinement       'Bruker SAINTPLUS'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'Bruker SAINTPLUS'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2014 (Sheldrick, 2014)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 2008)'
_diffrn_ambient_temperature      110(2)
_diffrn_measured_fraction_theta_full 0.974
_diffrn_measured_fraction_theta_max 0.975
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0427
_diffrn_reflns_av_unetI/netI     0.0494
_diffrn_reflns_Laue_measured_fraction_full 0.974
_diffrn_reflns_Laue_measured_fraction_max 0.975
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       17
_diffrn_reflns_limit_l_min       -16
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_diffrn_reflns_point_group_measured_fraction_full 0.974
_diffrn_reflns_point_group_measured_fraction_max 0.975
_diffrn_reflns_theta_full        25.000
_diffrn_reflns_theta_max         26.459
_diffrn_reflns_theta_min         2.059
_exptl_absorpt_coefficient_mu    0.179
_exptl_absorpt_correction_T_max  0.813
_exptl_absorpt_correction_T_min  0.786
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   SADABS
_exptl_crystal_colour            yellow
_exptl_crystal_density_diffrn    1.334
_exptl_crystal_description       block
_exptl_crystal_F_000             512
_exptl_crystal_size_max          0.310
_exptl_crystal_size_mid          0.280
_exptl_crystal_size_min          0.112
_refine_diff_density_max         0.158
_refine_diff_density_min         -0.222
_refine_diff_density_rms         0.035
_refine_ls_extinction_method     none
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_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     313
_refine_ls_number_reflns         4851
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.023
_refine_ls_R_factor_all          0.0771
_refine_ls_R_factor_gt           0.0455
_refine_ls_shift/su_max          0.005
_refine_ls_shift/su_mean         0.001
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0485P)^2^+0.2015P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1098
_refine_ls_wR_factor_ref         0.1276
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3182
_reflns_number_total             4851
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            np9b00773_si_003.cif
_cod_data_source_block           kp61
_cod_original_cell_volume        1208.84(18)
_cod_database_code               1557632
_shelx_estimated_absorpt_t_min   0.947
_shelx_estimated_absorpt_t_max   0.980
_shelxl_version_number           2014-3
_shelx_res_checksum              67283
_shelx_hkl_checksum              89828