Patents - Redoxoma

The Center for Research on Redox
Processes in Biomedicine
CEPID Redoxoma
Patents
Support:
The Research Center of Redox Processes in Biomedicine, the
CEPID Redoxoma, is a network involving 24 researchers from the
State of São Paulo and several collaborators, including
international researchers. Its headquarters is the Instituto de
Química, Universidade de São Paulo and it has 19 other member
Institutions. The network is funded by São Paulo Research
Foundation, FAPESP, through CEPID program (Research, Innovation
and Dissemination Centers).
Mission: To investigate the mechanisms by which oxidants and
radicals act as mediators of physiological and pathophysiological
networks attempting to transfer the research results to
commercially and/or socially relevant applications, as well as to
education and dissemination of knowledge.
Oxidants and free radicals are produced in organisms by oxidation
and reduction processes (redox).
The health depends on perfect regulation of redox processes.
Deregulation of redox processes lead to diseases, including chronic
diseases.
The study of redox processes can elucidate disease mechanisms
and reveal new therapeutic targets. In practical terms can lead to
the design of novel therapeutic, nutritional and environmental
strategies and to the development/improvement of industrialized
products.
Metal complexes with indole or oxindole and
respective oxindolimine derivatives as potential
antiparasite agents
Patent protected under code BR 10 2013 026558-6, INPI/SP, 15/10/2013.
Inventors: Ana Maria da Costa Ferreira, Gustavo L. Sabino, Ricardo A. Couto,
Queite A. de Paula, Bruno S. Dario (IQ-USP, São Paulo); Grazielle A. Ribeiro and
Leda Q. Vieira (UFMG, Belo Horizonte).
Applications and targets
Selectivity Index
Antiparasite
Antiparasitemetallodrugs,
metallodrugs,alternative
alternativedo
dousual
usualdrugs
drugs
Anti-chagasic
Anti-chagasicagents
agents(T.
(T.cruzi)
cruzi)
Anti-leishmaniose
Anti-leishmanioseagents
agents(L.
(L.amazonensis)
amazonensis)
24h
48h
[Cu(isapn)](ClO4)2
4.8
11.6
[Cu(isaepy)2](ClO4)2
3.7
5.4
[Zn(isapn)]ClO4
5.6
12.4
[Zn(isaepy)Cl2]
2.0
3.2
Basic studies
tests
testsin
invitro:
vitro:against
against
different
differentforms
formsof
ofparasite
parasite
(trypomastigotes
(trypomastigotesand
and
amastigotes)
amastigotes)
Amastigotes/Total Macrophages
Development step
24 hours
1.0
0.8
0.6
0.4
0.2
0.0
1
2
3
4
5
6
7
8
9
10
11
12
Control
2+
-1
[Cu(isapn)] (12.6μmol.L )
2+
-1
[Cu(isapn)] (25.2μmol.L )
2+
-1
[Cu(isaepy)2] (9.8μmol.L )
2+
-1
[Cu(isaepy)2] (19.6μmol.L )
+
-1
[Zn(isapn)] (60.5μmol.L )
+
-1
[Zn(isapn)] (80.6μmol.L )
+
-1
[Zn(isapn)] (120.9μmol.L )
-1
[Zn(isaepy)Cl2] (77.4μmol.L )
-1
[Zn(isaepy)Cl2] (103.2μmol.L )
-1
[Zn(isaepy)Cl2] (154.8μmol.L )
-1
Benznidazole (192.1μmol.L )
Tropical diseases as Chagas, and Leishmaniose have been neglected for
many years, regarding the development of new, more efficient and less
toxic therapeutic drugs. Studies with the aim of preparing and
characterizing metallodrugs showing remarkable activity against
parasites that cause such diseases were developed, combining the
inhibitory capacity of indole derivative ligands towards specific proteins
(kinases and topoisomerases) and the redox properties of essential
metals (as copper). Our goal was to get metallodrugs more efficient and
less toxic then presently used drugs; and verify possible mechanisms of
action of such metallodrugs.
CEPID Redoxoma - 1
Antitumor compounds, processes for its production
and uses
Patent protected under code BR 10 2015 001045-1, INPI/SP, 16/01/2015.
Inventors: Esther Escribano Aranda, Ana Maria da Costa Ferreira, Koiti Araki,
Tiago Araújo Matias (IQ-USP, São Paulo); Carolina Portela Luz and Fábio Luiz
Navarro Marques (FM-USP, São Paulo).
Alternative metallodrugs containing copper and platinum ions,
coordinated to an adequate ligand, were isolated by a novel process,
with the aim of combine the redox properties of copper ions, and the
strong binding of platinum ions to DNA to obtain better antitumor
agents. As ligands, multifunctional derivatives of oxindolimine were
used, capable of inhibiting topoisomerases and quinases (as CDK1/Cyclin
B), and consequently induce apoptosis. The citotoxicity of these new
compounds against tumor cells were similar or higher than that of
cisplatin, a traditional metallodrug with high toxicity, colateral effects
and developed resistance.
CEPID Redoxoma - 2
Antiviral against Foot-and-mouth disease
Patent protected under code BR 10 2015 006561-2, INPI/SP, 24/03/2015,
“Método de identificação de compostos antivirais, compostos antivirais, método de
avaliação da funcionalidade dos compostos antivirais, uso dos compostos antivirais
composição farmacêutica antiviral”.
Inventors: Antonia Tavares do Amaral, Erika Piccirillo (IQ-USP, São Paulo);
Maria Aparecida Juliano and Marcia Yuri Kondo (UNIFESP, São Paulo).
Set of
Compounds
Docking
Activity
against
pro
Lb
Inhibitors
N
Asn46
Leu143
Glu147
His148
H
N
H
N
Ala149
O
O
Foot-and-mouth disease (FMD) is a highly contagious viral infection of
cloven-hoofed animals, such as cattle, sheep, goats, deer and pig. This
infection leads to the slaughter of thousand of infected and in-contact
animals, causing a significant economic impact in the infected areas. In
Brazil, the prophylactic treatment is made through mandatory animal
vaccination, applied every six months, from three months old animals.
Goals: The hereby invention consists on a method of identification of
compounds which have inhibitory activity evaluated against FMD virus
leader protease (Lbpro), bearing at least one electrophilic center,
particularly a nitrile group. It is a pharmaceutical composition which
contains a small and non-peptide inhibitor of leader protease (Lbpro), with
potential application against FMD infection.
CEPID Redoxoma - 3
QSAR approaches applied to rational design of
antibacterials, evaluated against Saccharomyces
cerevisiae (BY4741) and Escherichia coli (DH5α)
Patent protected under code PI 1000927-2 A2, INPI/SP, 11/03/2010,
“Composição antimicrobiana, método de inibição de microorganismos, uso de cloretos de
N,N[(dimetilamino)etil] benzoatos substituídos e método de avaliação da funcionalidade de
antimicrobianos”.
Inventors: Antonia Tavares do Amaral, Elba Vieira Mustafa dos Santos (IQUSP, São Paulo); Luis Eduardo Soares Netto and Gisele Monteiro de Souza (IBUSP, São Paulo).
R2
(CH2)n H
R3
R1
+
N R4
R5
R6
-
R1
Set of procain analogs, synthesized in the group, showing
antimicrobial activities evaluated against Saccaromyces
cerevisiae (BY4741) and Escherichia coli (DH5α), design by QSAR
approaches.
Problem : The spread of multi-resistant infections represents a
continuously growing problem to public health. Nowadays, search of
novel compounds, showing activity against Multidrug-resistant
microorganims becomes a real need. Literature studies indicated that
compounds having local anesthetics structure showed also antimicrobial
activity, against a wide spectrum of microorganisms.
Solution: QSAR approaches applied to rational design of antibacterials,
evaluated against Saccharomyces cerevisiae (BY4741) and Escherichia coli
(DH5α).
CEPID Redoxoma - 4
Screening method for modulators of cysteine
proteases activity and related pharmaceutical
composition
Patent protected under code PI 0805492-4A2, INPI/SP, 02/12/2008,
“Método para triagem de moduladores da atividade de cisteíno-proteases e composição
farmacêutica compreendendo os mesmos”.
Inventors: Antonia Tavares do Amaral, Alberto Malvezzi and Leandro de
Rezende (IQ-USP, São Paulo).
O
-
O
N
H
H
Virtual Screening: pharmacophore
flter → physico-chemical flter →
docking-flter → visual inspection
→ purchase → Enzymatic Assay
O
H
H
N
O
O
Br
Chemical structure of the compound ZINC01794422 identifed as
cruzain inhibitor by virtual screening.
Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of
the most serious amongst the so-called neglected diseases in Latin
America, specially in Brazil. So far there has been no effective treatment
for the chronic phase of this disease. Cruzain is a major cysteine protease
of T. cruzi and it is recognized as a valid target for Chagas disease
chemotherapy. The mechanism of cruzain action is associated with the
nucleophilic attack of an activated sulfur atom towards electrophilic
groups. In this report, features of a putative pharmacophore model of
the enzyme, developed as a virtual screening tool for the selection of
potential cruzain inhibitors, are described. The final proposed model was
applied to the ZINC v.7 database and afterwards experimentally
validated by an enzymatic inhibition assay. One of the compounds
selected by the model showed cruzain inhibition in the low micromolar
range.
CEPID Redoxoma - 5
Porphyrin derivatives, procedure for obtaining them
and the pharmaceutical composition containing
them
Patent deposited in INPI at 19/08/2008, under code PI 0802649-1 A2. Today patent is
under technical evaluation and technology is ready for transfer.
Inventors: Mauricio da Silva Baptista and Adjaci Uchoa Fernandes.
The present invention belongs to the field of compounds derived from
porphyrins. Specifically, the derivatives of the present invention are
photochromic compounds and may be used in Photodynamic Therapy.
The preparation process of the compounds of the present invention
comprises a final methylation step and optionally comprises using as the
starting compound a chlorophyllin, specifically a chlorophyllin which is
previously subjected to a metal/copper removing step. The invention
further comprises pharmaceutical compositions containing such
compounds that can be used in treating diseases like cancer, rheumatoid
arthritis, psoriasis, among other possible ones.
CEPID Redoxoma - 6
Composition of a surface collector agent and the
procedure for obtaining it
Patent deposited in INPI at 06/10/2009, under code PI 0905673-4 A2. Today patent is
under technical evaluation and technology is ready for transfer.
Inventors: Marcos Eduardo Sedra Gugliotti, Vinicius Curcino Carvalho Vieira,
Mauricio da Silva Baptista and Divinomar Severino.
The present invention concerns a surface collector agent composition
capable of confining and contract oil slicks and its derivatives scattered
on the surface of the water. The composition of this invention consists
solely of one or more surfactants belonging to the group of fatty acids
containing from 7 to 14 carbon atoms in their molecules. The
composition of this invention does not use organic solvents or other
substances harmful to the environment and has low toxicity. In one of its
preferred forms, the composition of this invention generates a
monomolecular film with a surface pressure of 70 mN/m, which spreads
rapidly over the water and is able to confine oil slicks in the form of
lenses with more than 0.5 cm thick for about 48 hours.
CEPID Redoxoma - 7
Polymer formulations for the treatment of skin
tumors by photodynamic therapy
Patent was deposited in INPI at 16/04/2010, under code PI 1001299-0 A2. Today patent is
under technical evaluation and technology is ready for transfer.
Inventors: Mauricio da Silva Baptista, Eduardo Caritá, Henrique Eisi Toma,
Daiana Kotra Deda and Koiti Araki.
The present invention relates to the preparation of polymeric
compositions for treatment of skin tumors using photodynamic therapy,
consisting of nano/micro capsules containing encapsulated photoactive
agents. This invention seeks to treat skin cancer by photodynamic
therapy based on the injection "in situ" of the polymeric formulations. In
this regard, the results obtained to date indicate the potential
application of these formulations in the therapeutic procedure aiming
beyond the treatment of tumors, also other skin diseases such as
psoriasis, vitiligo and leishmaniasis, as well as for applications with
cosmetic purposes.
CEPID Redoxoma - 8
Methods for obtaining porphyrin derivatives, chlorin
compounds, their pharmaceutical composition and
their use in photodynamic therapy
Patent was deposited in INPI at 11/02/2011, under code PI 1100371-5 A2. Today patent is
under technical evaluation and technology is ready for transfer.
Inventors: Mauricio da Silva Baptista, Osvaldo Antonio Serra, Yassuko
Iamamoto, Adjaci Uchoa Fernandes and Kleber Thiago de Oliveira.
The present invention describes a new method for obtaining porphyrin
and chlorin derivatives, which are sterically hindered avoiding the
formation of aggregation states and pharmaceutical composition
containing these compounds. Additionally, the present application
provides the use of these compounds in the preparation of
pharmaceutical compositions indicated for the Photodynamic Therapy
(PDT), particularly, cancer, inflammatory processes, such as, rheumatoid
arthritis, psoriasis, among others.
CEPID Redoxoma - 9
CEPID Redoxoma – CONTACT
Instituto de Química, Universidade de São Paulo
Av. Prof. Lineu Prestes, 748, Bloco 5 inferior, Sala 500
Butantan – São Paulo, SP – Brazil – 05508-000
Phone: +55-11-2648-0855
Email: [email protected]
CEPID Redoxoma homepage
http://redoxoma.iq.usp.br
Redoxoma Newsletter
Cover photo: Marcos Santos/USP Imagens
http://redoxomanewsletter.iq.usp.br
Support: Proc. FAPESP 2013/07937-8