Photodynamic therapy (PDT) is a promising therapy that involves the combination of light and photosensitizer (light-sensitive drug) to treat diseases characterized by rapidly growing tissues such as cancers. Over the years many tetrapyrrolic macrocycles, e.g. porphyrins, chlorins, phthalocyanines, porphycenes, benzoporphyrins and benzochlorins have been synthesized and evaluated for PDT activities. In this thesis, the aim is to develop new pyrrolic chroinophores and to study their potential use as photosensitizers for PDT. Corrole and Furochlorophin were chosen as the target compounds to achieve the aim....[ Read more ]

Photodynamic therapy (PDT) is a promising therapy that involves the combination of light and photosensitizer (light-sensitive drug) to treat diseases characterized by rapidly growing tissues such as cancers. Over the years many tetrapyrrolic macrocycles, e.g. porphyrins, chlorins, phthalocyanines, porphycenes, benzoporphyrins and benzochlorins have been synthesized and evaluated for PDT activities. In this thesis, the aim is to develop new pyrrolic chroinophores and to study their potential use as photosensitizers for PDT. Corrole and Furochlorophin were chosen as the target compounds to achieve the aim.

Corrole is a porphyrin analogue with one missing methine carbon. The corrole macrocycle is an effective photosensitizer and shares many of the same photochemical properties of the porphyrin ring, but with decreased chemical stability. In an effort to develop new PDT agents possessing less skin photosensitivity, we have investigated the corrole-type compounds as PDT agents. Several trans-A₂B-corroles and A₃-corroles with side chains containing polar and/or charged groups were successfully synthesized in this thesis.

Furochlorophin is a tetraazamacrocycle consisting of three pyrrole units with an exocyclic furan ring. Little is known about the chemistry of furochlorophin. Because of the desirable long-wavelength absorption characteristics of furochlorophin, it may be potentially applied as a second-generation photosensitizer for PDT. Several furochlorophin derivatives equipped with functional side chains have been synthesized in this work.

We are particularly interested in the application of PDT to nasopharyngeal carcinoma (NPC) since this disease has a high occurrence in the South China region, and also the fact that the nasopharynx is easily accessible by endoscopy and amenable to PDT treatment. Phototoxicity of the new synthetic corrole derivatives has been screened on a NPC cell line. Our results indicate that a corrole containing an o-hydroxy phenyl substituent exhibits the best activity. Confocal microscopy revealed that the site of localization is predominantly in mitochondria. Furthermore, nuclear staining revealed that DNA condensation and fragmentation occurred post-photodynamic therapy, indicating the cell death was in the apoptotic mode.