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S e p t e m b e r 1 0 - 1 1 , 2 0 1 8 | D u b l i n , I r e l a n d
Pharma Chem Congress 2018 & Toxicology Congress 2018
Note:
Page 15
allied
academies
TOXICOLOGY AND PHARMACOLOGY
PHARMACEUTICAL CHEMISTRY & DRUG DISCOVERY
&
Global Congress on
International Conference on
Joint Event on
Asian Journal of Biomedical and Pharmaceutical Sciences
|
Volume 8
Larisa Klapshina, Asian J Biomed Pharmaceut Sci 2018, Volume 8 | DOI: 10.4066/2249-622X-C2-004
MULTIFUNCTIONAL ANTICANCER DRUGS FOR
PERSONALIZED MEDICINE BASED ON CYANO-
ARYL PORPHYRIZING PIGMENTS: EFFICIENT
PHOTOSENSITIZERS IN PDT AND NEW TYPE OF
FLUORESCENT MOLECULAR ROTORS FOR REAL-
TIME MONITORING OF PDT TREATING
F
or a long time, the idea of separated diagnostic and therapeutic approaches
was predominant in the development of new drugs in medicine. However,
recently a significant increase has been observed in the trend to create the
drugs which effectively combine diagnostic and therapeutic approaches. The
development of multifunctional agents which allows effective therapy and
non-invasive real-time monitoring of individual therapeutic response to the
treatment procedure is an important challenge for modern pharmaceutical
chemistry. Here we report the new series of novel aryl-cyano porphyrazine
pigments containing heteroatoms (O, N, S) in the aromatic groups in the
peripheral frame of macrocycle. We established that design of aryl substituents
framing macrocycle provides a fine-tuning of photophysical and photodynamic
properties of cyano-aryl porphyrazine pigments.
In vivo
experiments showed
selective accumulation of porphyrazine in tumor that was indicated by higher
fluorescence intensity in the tumor area in comparison with the normal tissues.
High efficiency of cyano-aryl porphyrazine free bases as photosensitizers
had been demonstrated by experiments
in vivo
on PDT of the CT26 tumors.
Moreover, this series of tetrapyrroles showed the strong dependence of the
fluorescence parameters (quantum yield and fluorescence life time) on the
local viscosity. Such the dyes termed fluorescent molecular rotors (FMR)
are very promising agents for optical sensing of intracellular viscosity. Since
viscosity and diffusion rate in the domains of live cells define functional state
of cells such the sensing allows, in principle, real-time monitoring of the
tumor response to therapeutic procedure. We first proposed theoretical model
describing the FMR properties of novel porphyrazine series as the unique
example of FMR photophysical behavior originated within porphyrazine annular
structure. The model is based on the twisted intramolecular charge transfer
(TICT) mechanism upon photoexcitation and arises from segmental mobility of
several potentially rotatable π-donor aryl groups which alternate with strongly
electron withdrawing CN-groups. We believe that innovative cyano-aryl
porphyrazines we developed are very promising for personalized medicine as
photosensitizers in PDTwith additional function of real-time optical monitoring
of the tumor response to PDT treatment.
Biography
Larisa Klapshina has received her PhD fromRazuvaev
Institute of Organometallic Chemistry of Russian
Academy of Sciences, IOMC RAS (Nizhny Novgorod,
Russia). Currently, she is a Senior Researcher at IOMC
RAS. She and her group work in organic and organo-
metallic synthesis and functional materials in bio-
photonics and biomedicine. She is author of about
100 articles.
klarisa@iomc.ras.ruLarisa Klapshina
Russian Academy of Sciences, Russia