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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 79| Part 11| November 2023| Pages 999-1002
https://doi.org/10.1107/S2056989023008526

Synthesis, crystal structure and in vitro anti-proliferative activity of 2-[(4-acetyl­phen­yl)carbamo­yl]phenyl acetate

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Reham A. Mohamed-Ezzat,a Benson M. Kariukib and Aladdin M. Srourc*

aChemistry of Natural & Microbial Products Department, National Research Centre, Cairo, Egypt, bSchool of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10, 3AT, United Kingdom, and cDepartment of Therapeutic Chemistry, National Research Centre, Dokki, Cairo, 12622, Egypt
*Correspondence e-mail: am.srour@nrc.sci.eg

Edited by G. Diaz de Delgado, Universidad de Los Andes Mérida, Venezuela (Received 22 November 2022; accepted 27 September 2023; online 5 October 2023)

2-[(4-Acetyl­phen­yl)carbamo­yl]phenyl acetate, C17H15NO4, has been synthesized and structurally characterized. In the structure, N—H⋯O hydrogen-bonding inter­actions form chains of mol­ecules aligned along the [101] direction. The chains are linked by π–π and C—H⋯π inter­actions, forming a three dimensional network. The compound has been screened for in vitro anti-proliferative activity revealing considerable activity.

CCDC reference: 2087303

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1. Chemical context

Acetyl­salicylic acid (ASA), or aspirin, is a non-steroidal anti-inflammatory drug (NSAID) utilized extensively as an analgesic and anti­pyretic agent. It has been shown to induce apoptotic cell death in several cancer cell lines (Brune & Patrignani, 2015[Brune, K. & Patrignani, P. (2015). J Pain Res. pp. 105-118.]; Ranger et al., 2020[Ranger, G. S., McKinley-Brown, C., Rogerson, E. & Schimp-Manuel, K. (2020). Permanente J. 24, 19.116.]; Abd-El-Aziz et al., 2021[Abd-El-Aziz, A. S., Benaaisha, M. R., Abdelghani, A. A., Bissessur, R., Abdel-Rahman, L. H., Fayez, A. M. & El-ezz, D. A. (2021). Biomolecules, 11, 1568.]). Aspirin is one of the most prescribed drugs for pain relief as well as for cardiovascular prophylaxis. Decades of investigations have provided substantial evidence indicating potential in the prevention of cancer, particularly colorectal cancer (Drew et al., 2016[Drew, D. A., Cao, Y. & Chan, A. T. (2016). Nat. Rev. Cancer, 16, 173-186.]). Comprehensive clinical benefits of aspirin-based chemoprevention strategies have lately been acknowledged. However, due to the identified risks of long-term aspirin usage, larger scale adoption of an aspirin chemoprevention strategy is likely to involve enhanced identification of individuals for whom the protective benefits compensate the side effects (Drew et al., 2016[Drew, D. A., Cao, Y. & Chan, A. T. (2016). Nat. Rev. Cancer, 16, 173-186.]). Aspirin is recognized as a means for prevention of ischemic heart attack and stroke (Pinto et al., 2013[Pinto, A., Di Raimondo, D., Tuttolomondo, A., Buttà, C. & Licata, G. (2013). Curr. Vasc. Pharmacol. 11, 803-811.]). Although several effects of aspirin are related to its ability to inhibit cyclo­oxygenase (COX), a key enzyme in prostaglandin biosynthesis, COX-independent effects have also been reported (Alfonso et al., 2014[Alfonso, L., Ai, G., Spitale, R. C. & Bhat, G. J. (2014). Br. J. Cancer, 111, 61-67.]). Aspirin has emerged as a promising inter­vention in cancer treatment in the past decade (Tran et al., 2021[Tran, P. H. L., Lee, B. J. & Tran, T. T. D. (2021). Curr. Pharm. Des. 27, 2209-2220.]; Lichtenberger et al., 2019[Lichtenberger, L. M. & Vijayan, K. V. (2019). Cancer Res. 79, 3820-3823.]), and has a protective effect against several types of cancer (Garcia-Albeniz et al., 2011[Garcia-Albeniz, X. & Chan, A. T. (2011). Best Pract. Res. Clin. Gastroenterol. 25, 461-472.]; Usman et al., 2015[Usman, M. W., Luo, F., Cheng, H., Zhao, J. J. & Liu, P. (2015). Biochim. Biophys. Acta, 1855, 254-263.]). It induces cell death in various cancer cell lines, such as myeloid leukaemia and HeLa cells, chronic lymphocytic leukaemia cells, colon cancer cells (Bellosillo et al., 1998[Bellosillo, B., Piqué, M., Barragán, M., Castaño, E., Villamor, N., Colomer, D., Montserrat, E., Pons, G. & Gil, J. (1998). Blood, 92, 1406-1414.]), gastric cancer (Gu et al., 2005[Gu, Q., Wang, J. D., Xia, H. H., Lin, M. C., He, H., Zou, B., Tu, S. P., Yang, Y., Liu, X. G., Lam, S. K., Wong, W. M., Chan, A. O., Yuen, M. F., Kung, H. F. & Wong, B. C. (2005). Carcinogenesis, 26, 541-546.]), colorectal cancer (Stark et al., 2007[Stark, L. A., Reid, K., Sansom, O. J., Din, F. V., Guichard, S., Mayer, I., Jodrell, D. I., Clarke, A. R. & Dunlop, M. G. (2007). Carcinogenesis, 28, 968-976.]) and cholangiocarcinoma (Shen & Shen, 2021[Shen, X. & Shen, X. (2021). Int. J. Cancer, 148, 1323-1330.]).

Motivated by the properties enumerated above and in continuation of our inter­est in the synthesis of aspirin-based scaffolds, 2-[(4-acetyl­phen­yl)carbamo­yl]phenyl acetate was synthesized and characterized. It was anti­cipated that the compound would present biological activity and it was tested against an NCI 60 cell-line panel.

Facile synthesis of the target 2-[(4-acetyl­phen­yl)carbamo­yl]phenyl acetate (3) was carried out through the reaction of 4'-amino aceto­phenone (1) and 2-(chloro­carbon­yl)phenyl acetate (2) in the presence of a qu­anti­tative amount of triethyl amine (Fig. 1[link]). The chemical identity of the product was confirmed by various spectroscopic techniques consistent with literature reports (Gao et al., 2014[Gao, S., Xu, Z., Wang, X., Feng, H., Wang, L., Zhao, Y., Wang, Y. & Tang, X. (2014). Asian J. Chem. 26, 7157-7159.]; Eissa et al., 2017[Eissa, I. H., Mohammad, H., Qassem, O. A., Younis, W., Abdelghany, T. M., Elshafeey, A., Abd Rabo Moustafa, M. M., Seleem, M. N. & Mayhoub, A. S. (2017). Eur. J. Med. Chem. 130, 73-85.]).

[Scheme 1]
[Figure 1]
Figure 1
Synthetic route towards compound 3.

2. Structural commentary

The asymmetric unit is shown in Fig. 2[link]. The phenyl­ethanone fragment of the mol­ecule is essentially planar with a twist angle between the phenyl ring (C3–C8) and the acetaldehyde group (C1,C2,O1) of 4.7 (2)°. In the phenyl­acetate group of the mol­ecule, the acetate group (C16,C17,O3,O4) is almost perpendicular to the phenyl ring (C10–C15) with a twist angle of 82.39 (6)°. This relationship between the acetate group and the ring is similar to that found in aspirin (Tyler et al., 2020[Tyler, A. R., Ragbirsingh, R., McMonagle, C. J., Waddell, P. G., Heaps, S. E., Steed, J. W., Thaw, P., Hall, M. J. & Probert, M. R. (2020). Chem, 6, 1755-1765.]). The formamide group (C9,N1,O2) is twisted by 25.14 (14)° from one phenyl ring (C3–C8) and by 45.53 (8)° from the second (C10–C15). There is an intra­molecular C5—H5⋯O2 hydrogen bond (Table 1[link]).

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the C10–C15 ring.
D—H⋯A D—H H⋯A D⋯A D—H⋯A
C5—H5⋯O2 0.93 2.35 2.8792 (19) 116
C12—H12⋯O4i 0.93 2.59 3.396 (2) 145
N1—H1⋯O1ii 0.86 2.08 2.9181 (16) 164
C8—H8⋯Cg1iii 0.93 3.20 4.0960 (15) 164
Symmetry codes: (i) [-x+1, -y+2, -z]; (ii) [x-{\script{1\over 2}}, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]; (iii) [-x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+{\script{1\over 2}}].
[Figure 2]
Figure 2
The asymmetric unit of (3) showing displacement ellipsoids at the 50% probability level.

The twist angles between the various groups in the mol­ecule are similar to those of the N-(4-acetyl­phen­yl)benzamide moiety in N-(4-acetyl­phen­yl)-2-[(1,3-dioxo-1,3-di­hydro-2H-isoindol-2-yl)meth­yl]benzamide (Mourad et al., 2020[Mourad, A. A. E., Mourad, M. A. E. & Jones, P. G. (2020). Drug. Des. Dev. Ther. Vol. 14, 3111-3130.]).

3. Supra­molecular features

In the crystal, N—H⋯O hydrogen-bonding inter­actions occur between neighbouring mol­ecules related by −[{1\over 2}] + x, [{1\over 2}] − y, −[{1\over 2}] + z, resulting in chains parallel to the [101] direction (Fig. 3[link], Table 1[link]). A C12—H12⋯O4i hydrogen bond is also observed. Contacts of the type π–π are also observed between symmetry-related phenyl rings from neighbouring mol­ecules with centroid-to-centroid distances of 4.0823 (9) Å (C3–C8 rings, symmetry operation 1 − x, 1 − y, 1 − z) and 3.9417 (10) Å (C10–C15 rings, symmetry operation 1 − x, 1 − y, −z). Additionally, a C—H⋯π inter­action occurs between the edge of the C3–C8 ring and the face of the C10–C15 ring (Table 1[link]).

[Figure 3]
Figure 3
A segment of the crystal structure of compound 3 showing inter­molecular contacts (N—H⋯O in green, π–π and C—H⋯π in red).

4. Database survey

A search of the Cambridge Structural Database (Version 5.43, update of November, 2022; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) for structures containing the N-(4-acetyl­phen­yl)benzamide moiety pro­duced one hit for N-(4-acetyl­phen­yl)-2-[(1,3-dioxo-1,3-di­hydro-2H-isoindol-2-yl)meth­yl]benzamide (LACYIB; Mourad et al., 2020[Mourad, A. A. E., Mourad, M. A. E. & Jones, P. G. (2020). Drug. Des. Dev. Ther. Vol. 14, 3111-3130.]).

5. Synthesis and crystallization

Melting points were determined on a Stuart SMP30 melting-point apparatus. IR spectra (KBr) were recorded on a JASCO 6100 spectrophotometer. NMR spectra were recorded on a JEOL AS 500 (DMSO-d6, 1H: 500 MHz, 13C: 125 MHz) spectrometer, JEOL USA, Inc. Mass spectra were recorded on a Shimadzu GCMS-QP 1000 EX (EI, 70 eV) spectrometer, Shimadzu Corporation, Kyoto, Japan. Elemental micro analyses were performed using a Vario Elemental analyzer, Elementar Analysensysteme GmbH, Langenselbold, Germany. Figs. S1–S4 of the Supplementary material show the spectroscopic data. The starting compound 2-(chloro­carbon­yl)phenyl acetate (1) was prepared according to previously reported procedures (Sharma et al., 2011[Sharma, H., Patil, S., Sanchez, T. W., Neamati, N., Schinazi, R. F. & Buolamwini, J. K. (2011). Bioorg. Med. Chem. 19, 2030-2045.]; Ngaini et al., 2012[Ngaini, Z., Mohd Arif, M. A., Hussain, H., Mei, E. S., Tang, D. & Kamaluddin, D. H. (2012). Phosphorus Sulfur Silicon, 187, 1-7.]).

Synthesis of 2-[(4-acetyl­phen­yl)carbamo­yl]phenyl acetate (3)

To a stirred solution of 4′-amino­aceto­phenone (1) (1.35 g, 10 mmol) and triethyl amine (1.48 ml, 11 mmol) in 25 ml of di­chloro­methane, 2-(chloro­carbon­yl)phenyl acetate (2) (1.98 g, 10 mmol) was added portion-wise over a period of 30 min, and the mixture was stirred at room temperature for 6 h (Fig. 1[link]). The mixture was filtered, the solvent evaporated under reduced pressure, and then the solid obtained was washed with water, dried and recrystallized from benzene/pet. ether 60–80.

Buff-colored crystals; yield (2.65 g) 89%; mp 424–426 K; IR (νmax/cm−1): 3297 (NH), 1659, 1679, 1760 (C=O); 1H NMR (DMSO-d6) δ (ppm): 2.18 (s, 3H, CH3), 2.52 (s, 3H, COCH3), 7.24, 7.26 (dd, 1H, J = 1.20, 1.10 Hz, CH), 7.39 (t, 1H, J = 8.13 Hz, CH), 7.57 (t, 1H, J = 8.65 Hz, CH), 7.70, 7.71 (dd, 1H, J = 1.65, 1.65 Hz, CH), 7.85 (d, 2H, J = 8.8 Hz, CH), 7.94 (d, 2H, J = 8.8 Hz, CH), 10.71 (s, 1H, NH); 13C NMR (DMSO-d6) δ (ppm) 20.84, 26.60, 119.28, 123.48, 126.08, 129.37, 129.45, 129.53, 129.57, 132.03, 132.32, 143.64, 148.30, 164.80, 169.04, 196.74; MS: m/z (%) 297.88 (M+, 9.97); Analysis calculated for C17H15NO4 (297.31): C, 68.68; H, 5.09; N, 4.71. Found: C, 68.66; H, 5.10; N, 4.70.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. H atoms were positioned geometrically and refined as riding with Uiso(H) = 1.2 or 1.5Ueq(C,N).

Table 2
Experimental details

Crystal data
Chemical formula C17H15NO4
Mr 297.30
Crystal system, space group Monoclinic, P21/n
Temperature (K) 296
a, b, c (Å) 11.6286 (5), 8.6913 (4), 15.8180 (7)
β (°) 110.380 (5)
V (Å3) 1498.62 (12)
Z 4
Radiation type Cu Kα
μ (mm−1) 0.78
Crystal size (mm) 0.35 × 0.14 × 0.13
 
Data collection
Diffractometer Agilent SuperNova, Dual, Cu at home/near, Atlas
Absorption correction Gaussian (CrysAlis PRO; Rigaku OD, 2019[Rigaku OD (2019). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.])
Tmin, Tmax 0.390, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 17065, 3141, 2612
Rint 0.027
(sin θ/λ)max (Å−1) 0.632
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.043, 0.134, 1.03
No. of reflections 3141
No. of parameters 201
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.17, −0.16
Computer programs: CrysAlis PRO (Rigaku OD, 2019[Rigaku OD (2019). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]), SHELXS (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2019/3 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]) and Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]).

7. In vitro anti-proliferative activity against NCI 60 cell-lines panel

The title compound was selected by the National Cancer Institute (NCI), NIH, USA under the Developmental Therapeutic Program (DTP) for the estimation of in vitro anti­proliferative activity against the NCI 60 cell-line panel. This screen utilizes human tumour cell lines, representing melanoma, leukemia, colon, lung, ovary, brain, prostate, kidney and breast cancers.

The NCI screening service ranks compounds with a promising drug-like mode of action on the basis of computer-aided design. The capability of the submitted compounds to convey diversity to the NCI small mol­ecule compound collection is critical to selecting them for screening.

The title compound was assigned NCI code NSC D-832401 representing the chemotype of this work. It was screened at an initial 10 μM one-dose % inhibition assay on the full NCI 60 cell-line panel. The results are shown in Fig. 4[link]. The results are represented as cell growth % for the compound in each of the panels. The lowest cell-growth promotion was observed on leukemia RPMI-8226 cell line (GP = 92.72%), non-small-cell lung cancer NCI-H522 (GP = 94.57%), colon cancer HCT-15 (GP = 98.05%), CNS cancer SNB-75 (GP = 80.85%), melanoma MDA-MB-43 (GP = 95.29%), ovarian cancer OVCAR-4 (GP = 96.33%), renal cancer A498 (GP = 81.27%) and breast cancer T-47D (GP = 89.47%).

[Figure 4]
Figure 4
In vitro anti-proliferative activity data of compound 3 at 10−5 M.

Thus, in general, the compound displays considerable in vitro anti-proliferative activity at 10 μM against most of the tested cancer cell lines. This supports possible future experiments on this compound including the determination of IC50 (for the most promising cell line) and cytotoxicity in normal cells.

Supporting information

CCDC reference: 2087303

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989023008526/dj2060sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989023008526/dj2060Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989023008526/dj2060Isup3.cml

Supporting information file. DOI: https://doi.org/10.1107/S2056989023008526/dj2060sup4.docx

checkCIF report


Computing details top

Data collection: CrysAlis PRO 1.171.40.53 (Rigaku OD, 2019); cell refinement: CrysAlis PRO 1.171.40.53 (Rigaku OD, 2019); data reduction: CrysAlis PRO 1.171.40.53 (Rigaku OD, 2019); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL2019/3 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2020).

2-[(4-Acetylphenyl)carbamoyl]phenyl acetate top
Crystal data top
C17H15NO4F(000) = 624
Mr = 297.30Dx = 1.318 Mg m−3
Monoclinic, P21/nCu Kα radiation, λ = 1.54184 Å
a = 11.6286 (5) ÅCell parameters from 5304 reflections
b = 8.6913 (4) Åθ = 4.1–76.2°
c = 15.8180 (7) ŵ = 0.78 mm−1
β = 110.380 (5)°T = 296 K
V = 1498.62 (12) Å3Needle, yellow
Z = 40.35 × 0.14 × 0.13 mm
Data collection top
Agilent SuperNova, Dual, Cu at home/near, Atlas
diffractometer		2612 reflections with I > 2σ(I)
ω scansRint = 0.027
Absorption correction: gaussian
(CrysAlisPro; Rigaku OD, 2019)		θmax = 76.9°, θmin = 4.1°
Tmin = 0.390, Tmax = 1.000h = −14→14
17065 measured reflectionsk = −10→10
3141 independent reflectionsl = −19→19
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.043H-atom parameters constrained
wR(F2) = 0.134 w = 1/[σ2(Fo2) + (0.0761P)2 + 0.1892P]
where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max = 0.002
3141 reflectionsΔρmax = 0.17 e Å−3
201 parametersΔρmin = −0.16 e Å−3
0 restraints
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.5388 (2)0.1466 (3)0.63141 (13)0.0868 (6)
H1A0.5875980.1052440.6890020.130*
H1B0.4984870.0642120.5917390.130*
H1C0.4783720.2153980.6388330.130*
C20.61923 (14)0.23211 (19)0.59205 (9)0.0576 (4)
C30.56774 (12)0.29253 (17)0.49855 (9)0.0505 (3)
C40.64622 (13)0.36063 (19)0.46058 (10)0.0587 (4)
H40.7289420.3706910.4950500.070*
C50.60455 (13)0.41363 (19)0.37314 (10)0.0589 (4)
H50.6589150.4573510.3486380.071*
C60.48068 (12)0.40141 (16)0.32165 (8)0.0490 (3)
C70.40109 (13)0.3340 (2)0.35836 (10)0.0624 (4)
H70.3182080.3253270.3240400.075*
C80.44443 (13)0.2795 (2)0.44606 (10)0.0619 (4)
H80.3903860.2336330.4700960.074*
C90.48064 (13)0.56038 (17)0.19145 (9)0.0539 (3)
C100.41025 (12)0.58347 (17)0.09278 (9)0.0512 (3)
C110.38681 (13)0.73080 (17)0.05690 (10)0.0532 (3)
C120.32771 (14)0.7548 (2)−0.03390 (11)0.0629 (4)
H120.3117680.854402−0.0564850.075*
C130.29218 (15)0.6303 (2)−0.09134 (10)0.0668 (4)
H130.2529950.646157−0.1528720.080*
C140.31454 (15)0.4827 (2)−0.05786 (10)0.0634 (4)
H140.2910760.398867−0.0966450.076*
C150.37213 (14)0.45989 (19)0.03382 (10)0.0574 (4)
H150.3855670.3601300.0563970.069*
C160.52387 (15)0.93013 (18)0.12475 (11)0.0606 (4)
C170.5436 (2)1.0612 (2)0.18968 (14)0.0858 (6)
H17A0.5594861.0216280.2493460.129*
H17B0.4716101.1246740.1725430.129*
H17C0.6124951.1212220.1888000.129*
N10.43273 (11)0.45087 (15)0.23117 (7)0.0547 (3)
H10.3661610.4072570.1974900.066*
O10.72755 (11)0.25066 (17)0.63648 (8)0.0776 (4)
O20.57285 (12)0.63430 (15)0.23103 (8)0.0745 (4)
O30.41633 (10)0.85821 (13)0.11491 (8)0.0629 (3)
O40.58982 (12)0.89231 (15)0.08529 (9)0.0739 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0814 (12)0.1205 (18)0.0571 (9)0.0023 (11)0.0223 (9)0.0268 (10)
C20.0559 (8)0.0687 (9)0.0445 (7)0.0146 (6)0.0127 (6)0.0053 (6)
C30.0473 (7)0.0592 (8)0.0412 (6)0.0072 (5)0.0108 (5)0.0026 (5)
C40.0424 (7)0.0737 (10)0.0497 (7)−0.0019 (6)0.0030 (5)0.0093 (6)
C50.0461 (7)0.0745 (10)0.0496 (7)−0.0079 (6)0.0087 (6)0.0102 (6)
C60.0478 (7)0.0533 (7)0.0391 (6)−0.0021 (5)0.0067 (5)0.0010 (5)
C70.0422 (7)0.0892 (11)0.0470 (7)−0.0061 (7)0.0045 (5)0.0094 (7)
C80.0470 (7)0.0872 (11)0.0497 (7)−0.0017 (7)0.0146 (6)0.0110 (7)
C90.0555 (7)0.0560 (8)0.0444 (7)−0.0038 (6)0.0101 (6)0.0016 (5)
C100.0477 (7)0.0579 (8)0.0452 (7)−0.0002 (5)0.0127 (5)0.0061 (6)
C110.0479 (7)0.0588 (8)0.0545 (7)0.0020 (6)0.0198 (6)0.0055 (6)
C120.0563 (8)0.0691 (10)0.0619 (9)0.0089 (7)0.0190 (7)0.0216 (7)
C130.0589 (8)0.0881 (12)0.0467 (7)−0.0016 (8)0.0102 (6)0.0154 (7)
C140.0633 (9)0.0749 (10)0.0465 (7)−0.0083 (7)0.0122 (6)−0.0003 (7)
C150.0595 (8)0.0576 (8)0.0495 (7)−0.0028 (6)0.0118 (6)0.0045 (6)
C160.0676 (9)0.0522 (8)0.0618 (8)0.0008 (6)0.0223 (7)0.0114 (6)
C170.1228 (17)0.0633 (10)0.0751 (12)−0.0140 (11)0.0391 (12)−0.0023 (9)
N10.0501 (6)0.0636 (7)0.0401 (6)−0.0099 (5)0.0029 (4)0.0047 (5)
O10.0566 (7)0.1113 (11)0.0531 (6)0.0140 (6)0.0042 (5)0.0188 (6)
O20.0769 (8)0.0774 (8)0.0537 (6)−0.0279 (6)0.0031 (5)0.0077 (5)
O30.0680 (7)0.0566 (6)0.0695 (7)0.0020 (5)0.0307 (5)0.0010 (5)
O40.0680 (7)0.0697 (8)0.0905 (9)−0.0052 (5)0.0356 (7)0.0014 (6)
Geometric parameters (Å, º) top
C1—C21.490 (3)C9—C101.5022 (18)
C1—H1A0.9600C10—C111.389 (2)
C1—H1B0.9600C10—C151.390 (2)
C1—H1C0.9600C11—C121.375 (2)
C2—O11.221 (2)C11—O31.4024 (18)
C2—C31.4848 (18)C12—C131.380 (3)
C3—C41.388 (2)C12—H120.9300
C3—C81.3890 (19)C13—C141.378 (2)
C4—C51.3759 (19)C13—H130.9300
C4—H40.9300C14—C151.384 (2)
C5—C61.3902 (19)C14—H140.9300
C5—H50.9300C15—H150.9300
C6—C71.382 (2)C16—O41.191 (2)
C6—N11.4101 (16)C16—O31.358 (2)
C7—C81.384 (2)C16—C171.497 (3)
C7—H70.9300C17—H17A0.9600
C8—H80.9300C17—H17B0.9600
C9—O21.2194 (18)C17—H17C0.9600
C9—N11.3619 (19)N1—H10.8600
C2—C1—H1A109.5C11—C10—C9120.41 (13)
C2—C1—H1B109.5C15—C10—C9121.66 (13)
H1A—C1—H1B109.5C12—C11—C10121.50 (14)
C2—C1—H1C109.5C12—C11—O3118.87 (14)
H1A—C1—H1C109.5C10—C11—O3119.49 (12)
H1B—C1—H1C109.5C11—C12—C13119.64 (15)
O1—C2—C3120.27 (15)C11—C12—H12120.2
O1—C2—C1119.83 (14)C13—C12—H12120.2
C3—C2—C1119.89 (14)C14—C13—C12120.25 (14)
C4—C3—C8118.28 (12)C14—C13—H13119.9
C4—C3—C2118.95 (13)C12—C13—H13119.9
C8—C3—C2122.74 (14)C13—C14—C15119.59 (15)
C5—C4—C3121.56 (13)C13—C14—H14120.2
C5—C4—H4119.2C15—C14—H14120.2
C3—C4—H4119.2C14—C15—C10121.16 (15)
C4—C5—C6119.58 (14)C14—C15—H15119.4
C4—C5—H5120.2C10—C15—H15119.4
C6—C5—H5120.2O4—C16—O3123.25 (16)
C7—C6—C5119.67 (13)O4—C16—C17126.61 (17)
C7—C6—N1118.01 (12)O3—C16—C17110.13 (15)
C5—C6—N1122.28 (13)C16—C17—H17A109.5
C6—C7—C8120.17 (13)C16—C17—H17B109.5
C6—C7—H7119.9H17A—C17—H17B109.5
C8—C7—H7119.9C16—C17—H17C109.5
C7—C8—C3120.73 (14)H17A—C17—H17C109.5
C7—C8—H8119.6H17B—C17—H17C109.5
C3—C8—H8119.6C9—N1—C6126.92 (12)
O2—C9—N1124.00 (13)C9—N1—H1116.5
O2—C9—C10121.78 (13)C6—N1—H1116.5
N1—C9—C10114.22 (12)C16—O3—C11116.38 (12)
C11—C10—C15117.84 (13)
O1—C2—C3—C44.4 (2)C9—C10—C11—C12176.85 (13)
C1—C2—C3—C4−174.76 (17)C15—C10—C11—O3175.68 (13)
O1—C2—C3—C8−177.69 (16)C9—C10—C11—O3−7.6 (2)
C1—C2—C3—C83.1 (2)C10—C11—C12—C13−1.0 (2)
C8—C3—C4—C5−0.4 (2)O3—C11—C12—C13−176.59 (14)
C2—C3—C4—C5177.60 (15)C11—C12—C13—C140.7 (2)
C3—C4—C5—C61.1 (3)C12—C13—C14—C150.4 (3)
C4—C5—C6—C7−1.0 (2)C13—C14—C15—C10−1.3 (2)
C4—C5—C6—N1−178.77 (15)C11—C10—C15—C141.1 (2)
C5—C6—C7—C80.2 (3)C9—C10—C15—C14−175.65 (14)
N1—C6—C7—C8178.10 (15)O2—C9—N1—C6−1.7 (3)
C6—C7—C8—C30.5 (3)C10—C9—N1—C6178.01 (13)
C4—C3—C8—C7−0.4 (3)C7—C6—N1—C9156.85 (16)
C2—C3—C8—C7−178.31 (16)C5—C6—N1—C9−25.3 (2)
O2—C9—C10—C11−43.7 (2)O4—C16—O3—C112.0 (2)
N1—C9—C10—C11136.62 (15)C17—C16—O3—C11−178.92 (13)
O2—C9—C10—C15132.97 (18)C12—C11—O3—C16−85.66 (17)
N1—C9—C10—C15−46.7 (2)C10—C11—O3—C1698.63 (16)
C15—C10—C11—C120.1 (2)
Hydrogen-bond geometry (Å, º) top
Cg1 is the centroid of the C10–C15 ring.
D—H···AD—HH···AD···AD—H···A
C5—H5···O20.932.352.8792 (19)116
C12—H12···O4i0.932.593.396 (2)145
N1—H1···O1ii0.862.082.9181 (16)164
C8—H8···Cg1iii0.933.204.0960 (15)164
Symmetry codes: (i) −x+1, −y+2, −z; (ii) x−1/2, −y+1/2, z−1/2; (iii) −x+1/2, y−1/2, −z+1/2.
 

Acknowledgements

We are grateful for support by the National Research Center, Cairo, Egypt, and by Cardiff University, UK. We would like to thank the National Cancer Institute, NIH, USA for estimating the in vitro antiproliferative activity.

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ISSN: 2056-9890
Volume 79| Part 11| November 2023| Pages 999-1002
https://doi.org/10.1107/S2056989023008526
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