Developing Chlorin/Arylaminoquinazoline Conjugates with Nanomolar Activity for Targeted Photodynamic Therapy: Design, Synthesis, SAR, and Biological Evaluation.

In this report, we developed novel chlorin/arylaminoquinazoline conjugates for targeted photodynamic therapy of cancer. The synthesized photosensitizers consisted of chlorin- metallocomplexes (Zn, In, or Pd) conjugated with arylaminoquinazoline ligands with high affinity for epidermal growth factor receptors (EGFR). Additionally, the selectivity and antitumor properties of the conjugates were investigated in the EGFR-expressing A431 human tumor cell line .

A first-in-class β-glucuronidase responsive conjugate for selective dual targeted and photodynamic therapy of bladder cancer.

In this report, we present a novel prodrug strategy that can significantly improve the efficiency and selectivity of combined therapy for bladder cancer. Our approach involved the synthesis of a conjugate based on a chlorin-e photosensitizer and a derivative of the tyrosine kinase inhibitor cabozantinib, linked by a β-glucuronidase-responsive linker. Upon activation by β-glucuronidase, which is overproduced in various tumors and localized in lysosomes, this conjugate released both therapeutic modules within targeted cells.

Water-Soluble Chlorin/Arylaminoquinazoline Conjugate for Photodynamic and Targeted Therapy.

A new water-soluble conjugate, consisting of a chlorin- photosensitizer part, a 4-arylaminoquinazoline moiety with affinity to epidermal growth factor receptors, and a hydrophilic β-d-maltose fragment, was synthesized starting from methylpheophorbide- in seven steps. The prepared conjugate exhibited low levels of dark cytotoxicity and pronounced photoinduced cytotoxicity at submicromolar concentrations in vitro, with an IC(dark)/IC(light) ratio of ∼368 and a singlet oxygen quantum yield of about 20%. In tumor-bearing Balb/c nude mice, conjugate preferentially accumulates in the tumor tissue.