High excimer-state emission in the H-type aggregate of a novel asymmetric perylene bisimide derivative, 6, with triethyleneglycol chains and lactose functionalization was achieved in water. Furthermore, its application for enhancing the visualization of transfer latent fingerprints from glass slides to the poly(vinylidene fluoride) (PVDF) membrane was explored, which showed clear images of the latent fingerprint in daylight and under 365 nm ultraviolet illumination.

Five innovative ternary copper(II) complexes [Cu(OH-PIP)(Phe)Cl](1), [Cu(OH-PIP)(Gly)(H 2 O)]NO 3 • 2H 2 O (2), [Cu(OH-PIP)(Ala)(Cl)]•H 2 O (3), [Cu(OH-PIP)(Met)]PF 6 •2H 2 O (4), and [Cu(OH-PIP)(Gln)(H 2 O)](Cl)• 3H 2 O (5) have been synthesized and characterized by infrared spectroscopy, elemental analysis, and single crystal X-ray diffraction analysis. X-ray crystallography indicates that all Cu atoms are five-coordinated in a square-pyramidal configuration. The complexes have been screened for cytotoxicity against human breast cancer cell lines MCF-7, MDA-MB-231, and CAL-51.The best anticancer activity is obtained with triple-negative breast cancer CAL-51 and MDA-MB-231 cell lines, with IC 50 values in the range of 0.082−0.69 μM. Importantly, the copper compounds were more effective than carboplatin at triggering cell death. Mechanistically, the complexes inhibit proteasomal chymotrypsin-like activity, and docking studies reveal their 20S proteasome binding sites. As a consequence, they cause the accumulation of ubiquitinated proteins, inhibit cell proliferation, and induce apoptosis. In addition, these copper complexes decrease the stemness of triple-negative breast cancer cells and have synergistic effects with CBP on TNBC cells, indicating their great potential as a novel therapy for triple-negative breast cancer.

In order to improve the antitumor potency and therapeutic margins of natural product sophoridine, its novel nitrogen mustard carbamate derivatives were designed and synthesized. In screening their in vitro activity, we found all the tested compounds were more potent against the highly aggressive triple‐negative breast cancer cell line MDA‐MB‐231. Cellular functional assays showed that representative compounds could induce G1‐phase arrest and trigger apoptosis, evidenced by the alteration of Bax, Bcl‐2, caspase‐3 and PARP levels. Furthermore, these compounds significantly enhanced the autophagic flux with increased expression of LC3‐II and Beclin‐1, as well as decreased level of p62, which may attribute to simultaneously inhibition of the phosphorylation of p70S6K, 4E‐BP1 and AKT, the key substrates of the mTOR signaling pathway. In vivo, two compounds revealed potent antitumor activity in mice bearing MDA‐MB‐231. Altogether, our work describes novel leads to yield more potent chemotherapeutics against triple‐negative breast cancers, possibly mesenchymal stem‐like subtype.

Novel mustard functionalized sophoridine derivatives were synthesized and evaluated for their cytotoxicity against of a panel of various cancer cell lines. They were shown to be more sensitive to S180 and H22 tumor cells with IC50 values ranging from 1.01–3.65 μM, and distinctly were more cytotoxic to cancer cells than normal cell L929. In addition, compounds 7a, 7c, and 7e displayed moderate tumor suppression without apparent organ toxicity in vivo against mice bearing H22 liver tumors. Furthermore, they arrested tumor cells in the G1 phase and induced cellular apoptosis. Their potential binding modes with DNA-Top I complex have also been investigated.

To elevate the potency of sophoridine, phosphoramidate mustard motif was incorporated to D‐ring opened sophoridine scaffold. A series of acyclic aryloxy phosphoramidate mustard functionalized sophoridine derivatives were synthesized and screened for cytostatic activity in a range of different tumor cell lines (S180, H22, K562, MCF‐7, SMMC‐7721, and LoVo). All these compounds were shown to be more sensitive to S180 and H22 cells with IC50 values ranging from 2.10 to 7.21 μM. In addition, all targeted derivatives distinctly are more cytotoxic to cancer cells than normal cell L929. Compounds 8b, 8c, 8d, and 8e displayed moderate tumor suppression without apparent organ toxicity in vivo against mice bearing H22 liver tumors. Their potential binding modes with DNA topoisomerase I complex have also been investigated.