Synthesis of A Novel Calix[3]carbazole Derivative and Its Recognition and Detection of 10-Hydroxycamptothecin

doi:10.6023/cjoc202407038

Abstract

The fluorescent molecule capable of recognizing 10-hydroxycamptothecin (HCPT), a broad-spectrum anti-tumor drug, is not only able to detect it, but also able to enhance its activity due to the improvement of the delivery. Therefore, the construction of highly selective fluorescent hosts of HCPT is valuable, but remains challenging. In this work, an amphiphilic carbazole macrocyclic molecule (3) was synthesized and the host-guest interaction between 3 and HCPT was studied by fluorescence spectroscopy, NMR, scanning electron microscopy and transmission electron microscopy. The results showed that 3 could recognize HCPT with a stoichiometric ratio of 2∶1 via the mechanism of fluorescence resonance energy transfer (FRET) and a binding constant of 1.26×10¹⁴ (mol/L)^－2. The detection of limit (LOD) is 11.7 nmol•L^－1. In addition, the complexation enhanced the activity of HCPT to inhibit the proliferation of MCF-7 (Michigan Cancer Foundation-7) cells in vitro, and the IC₅₀ value decreased by two orders of magnitude, indicating that 3 possessed the dual function of both fluorescence probe and molecular carrier, thus providing scientific basis for further research.

Key words: host-guest, fluorescent probe, calix[n]carbazole

Cite this article

Wenbo Zhang, Siming Su, Peng Yang. Synthesis of A Novel Calix[3]carbazole Derivative and Its Recognition and Detection of 10-Hydroxycamptothecin[J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1395-1401.

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Fig. & Tab. 12

Figure 1. Structural formula of (a) HCPT and (b) of calix[3]- carbazole

Figure 2. Synthesis route of 3 Reaction conditions: (a) 2-bromo-propanoicaciethylester, NaH, DMF; (b) (CH2O)n, FeCl3, DCE; (c) 1,2-benzenedimethanol, DDQ, DCM, 0 ℃; (d) Monoethanolamine, DMF, 80 ℃

Entry	Catalyst	Yield/%
1	ZnCl₂	0
2	FeCl₃	39.6
3	AlCl₃	5.3
4	BF₃•OEt₂	15.2

Table 1. Effects of catalysts on the yield of cyclozation

Entry	Solvent	Yield/%
1	DCM	39.8
2	DCE	46.7
3	TCM	23.3
4	CCl₄	19.2

Table 2. Effects of solvents on yiled of cyclozation

Figure 3. (a) UV-Vis of 3 and HCPT, (b) fluorescence of 3 and HCPT, and (c) fluorescence of 3 and UV-Vis of HCPT

Figure 4. (a) Forward fluorescence titration spectra of 3 and HCPT, and (b) reverse fluorescence titration spectra of 3 and HCPT

Figure 5. (a) Job’s Plot curve of 3 and HCPT, and (b) nonlinear fitting curve of 3 and HCPT

Figure 6. (A) Fluorescence titration spectrum calibration curve between F549 nm/F364 nm and the concentration of HCPT, and (B) comparison of F549 nm/F364 nm between guests and 3 (a) o-Phenanthroline, (b) 2,2'-bipyridine, (c) 4,4'-bipyridine, (d) (R)-naproxen, (e) (S)-naproxen, (f) acenaphthenequinone, (g) anthraquinone, (h) Ca2＋, (i) Co2＋, (j) Mg2＋, (k) Pb2＋, (l) Fe3＋, (m) podophyllotoxin, (n) matrine, (o) quinoline, (p) artemisinin, (q) santonin, (r) dihydroqinghaosu, (s) ursolicacid, (t) corydaline, (u) etoposide, (v) paclitaxel, (w) 10-hydroxycamptothecin.

Figure 7. NOESY of 3 [D2O/DMSO-d6 (V∶V=4∶6)]

Figure 8. Scanning electron microscope (SEM) images of (a) 3, (b) HCPT, (c) 3 and HCPT complexes

Figure 9. Transmission electron mcroscope (TEM) images of (a) 3, (b) HCPT, (c) 3 and HCPT complexes

Sample	IC₅₀/(μmol•L^－1)
3	>50
HCPT	0.21±0.03
3-HCPT	0.0026±0.0005

Table 3. IC50 values of samples

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