Russian Chemical Bulletin, International Edition, Vol. 66, No.11, pp. 2157—2164, November, 2017 2157
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2157—2164, November, 2017.
10665285/17/66112157 © 2017 Springer Science+Business Media, Inc.
Conjugates of natural chlorins and isobornylphenols with
a different length of the spacer between the chlorin and terpenephenolic
fragments: synthesis and antioxidant activity
I. S. Khudyaeva,
D. V. Belykh,
O. G. Shevchenko,
M. A. Maximova,
L. F. Zainullina,
Yu. V. Vakhitova,
O. V. Shchukina,
E. V. Buravlev,
I. Yu. Chukicheva,
and A. V. Kutchin
Institute of Chemistry, Komi Scientific Centre, Ural Branch of the Russian Academy of Sciences,
48 ul. Pervomayskaya, 167000 Syktyvkar, Russian Federation.
Fax: +7 (821) 221 8477. Email: firstname.lastname@example.org
Institute of Biology, Komi Scientific Centre, Ural Branch of the Russian Academy of Sciences,
28 ul. Kommunisticheskaya, 167982 Syktyvkar, Russian Federation.
Fax: +7 (821) 224 0163
Institute of Biochemistry and Genetics, Ufa Scientific Centre of the Russian Academy of Sciences,
71 prosp. Oktyabrya, 450054 Ufa, Russian Federation.
Fax: +7 (347) 235 6088
V. V. Zakusov Institute of Pharmacology,
8 ul. Baltiyskaya, 125315 Moscow, Russian Federation.
Fax: +7 (499) 151 1261
Conjugates containing chlorine and isobornylphenolic fragments, which are connected
by spacers of different lengths, were synthesized from methyl pheophorbide a. The toxicity
and antioxidant activity of the obtained compounds were studied. Derivatives of pyro
pheophorbide a containing the most distant from the macrocycle terpenephenolic fragment
combine a low toxicity with the high antioxidant activity, and are the most promising for
further designing of new medicinal agents for the treatment of diseases associated with
a disorder in oxidationreduction processes in the body.
Key words: methyl pheophorbide a, pyropheophorbide a, chlorin e
antioxidant activity (AOA), lipid peroxidation (LPO), human embryonic kidney cells 293
(HEK 293), SHSY5Y neuroblastoma cells, viability.
Synthesis and study of compounds with an antioxi
dant activity is of interest in the context of search for
new medicinal agents for the treatment of diseases asso
ciated with a disorder in oxidationreduction processes in
the body (radiation sickness, neurodegenerative and on
cological diseases, etc.).
Porphyrins with substituents,
which bring additional antioxidant properties, may be
promising in this aspect.
One of synthetic pathways
to obtain such porphyrins is a conjugation of the porphy
rin macrocycle with molecules, which have their own
antioxidant activity. Phenols with terpene substituents
possess such properties. Synthesis of such conjugates from
chlorophyll a derivatives has a number of significant ad
vantages, the most important of which are a relatively
low toxicity of these compounds
and the presence of
several reaction centers that are convenient for use with
preparative purposes. The biological activity of such con
jugates may depend not only on the structure of a terpene
phenolic fragment, but also on the manner of its conjuga
tion with the porphyrin macrocycle, in particular on the
position of the phenolic fragment in the macrocycle and
the length of a spacer connecting the porphyrin and ter
penephenol fragments. Taking all these facts into account,
in the present work we report on the synthesis of some
conjugates, containing chlorine and isobornylphenol frag
ments connected by spacers of various lengths, from me
thyl pheophorbide a 1 and the evaluation of toxicity and
an antioxidant activity (AOA) of the obtained compounds.
Results and Discussion
To conjugate chlorine fragments with a terpenephe
nol, an ester bond formation was carried out by using the
Mukaiyama reagent for activation of the carboxyl groups
in chlorins 2 and 3, and also by a onepot hydrolysis of the
ester group at the exocycle of methyl pheophorbide a 1
with subsequent esterification (the carboxyl group, formed
as a result of hydrolysis, was activated by the same re