Potential Antimalarials. XV. Di-Mannich Bases of 2-(7'-Chloroquinolin-4'-ylamino)phenol and 2-[7'-Bromo( and trifluoromethyl)-1',5'-naphthyridin-4'-ylamino]phenol

1992 ◽  
Vol 45 (10) ◽  
pp. 1651 ◽  
Author(s):  
GB Barlin ◽  
TMT Nguyen ◽  
B Kotecka ◽  
KH Rieckmann

A total of 26 di-Mannich base derivatives of 2-(7'-chloroquinolin-4'-ylamino)phenol and 2-[7'- bromo (and trifluoromethyl )-1',5'-naphthyridin-4'-ylino]phenol, such as 2-(7'-chloroquinolin- 4'-ylamino)-4,6-bis( piperidin-1″-ylmethyl )phenol, together with some 3- and 5-methyl derivatives and mono-Mannich analogues, have been prepared by condensation of the 4-chloro heterocycle with the appropriate Mannich base derivatives of 2-aminophenols. In in vitro tests against Plasmodium falciparum, many of the di-Mannich base derivatives of 2-(7'-chloroquinolin-4'-ylarnino)phenol exhibited activity comparable to or superior to chloroquine against the chloroquine -sensitive (FCQ-27) isolate, and vastly superior activity compared with chloroquine against the chloroquine -resistant (K-1) isolate. Strong antimalarial activity was also revealed in in vivo tests against Plasmodium vinckei vinckei in mice.

1993 ◽  
Vol 46 (1) ◽  
pp. 21 ◽  
Author(s):  
GB Barlin ◽  
TMT Nguyen ◽  
B Kotecka ◽  
KH Rieckmann

Di- and mono-Mannich base derivatives of 2(and 4)-[2(and 8)-trifluoromethylquinolin-4-ylamino]phenols have been prepared for comparison with the 7-trifluoromethyl isomers in tests for antimalarial activity. The order of activity in in vitro tests against the FC-27 ( chloroquine -sensitive) strain of Plasmodium falciparum was 7-CF3 >> 8-CF3 > 2-CF3.


1991 ◽  
Vol 44 (5) ◽  
pp. 677 ◽  
Author(s):  
GB Barlin ◽  
C Jiravinyu ◽  
JH Yan

The mono- Mannich bases 2-diethylaminomethyl-, 2-t-butylaminomethyl-, 2-(pyrrolidin-1-ylmethyl)-, 2-(piperidin-1-ylmethyl)-, 2-(3-and 4-methylpiperidin-1-ylmethyl)-, 2-(4-benzylpip- eridin-1-ylmethyl)- and 2-(4-benzylpiperazin-1-ylmethyl)-4-[7-bromo (and 7-trifluoromethyl)- 1,5-naphthyridin-4-ylamino]-5,6,7,8-tetrahydronaphthalen-1-ols have been prepared from 4- acetamido-5,6,7,8-tetrahydronaphthalen-1-ols by Mannich reactions followed by hydrolysis to the 4-amino compounds and condensation with the relevant 4-chloro heterocycle. The antimalarial activities of these compounds against the chloroquine -sensitive isolate (FCQ-27) of Plasmodium falciparum in vitro are reported; 4-(7-bromo-1,5-naphthyridin-4-yl)amino-2-(t- butylaminomethyl )-5,6,7,8-tetrahydronaphthalen-1-ol was about twice as active as chloroquine . In in vivo tests against Plasmodium vinckei vinckei in mice this compound exhibited significant activity. The 7-bromo compounds were more active than their 7-trifluoromethyl analogues.


1995 ◽  
Vol 23 (4) ◽  
pp. 491-496
Author(s):  
Hanna Tähti ◽  
Leila Vaalavirta ◽  
Tarja Toimela

— There are several hundred industrial chemicals with neurotoxic potential. The neurotoxic risks of most of these chemicals are unknown. Additional methods are needed to assess the risks more effectively and to elucidate the mechanisms of neurotoxicity more accurately than is possible with the conventional methods. This paper deals with general tasks concerning the use of in vitro models in the evaluation of neurotoxic risks. It is based on our previous studies with various in vitro models and on recent literature. The induction of glial fibrillary acidic protein in astrocyte cultures after treatment with known neurotoxicants (mercury compounds and aluminium) is discussed in more detail as an important response which can be detected in vitro. When used appropriately with in vivo tests and with previous toxicological data, in vitro neurotoxicity testing considerably improves risk assessment. The incorporation of in vitro tests into the early stages of risk evaluation can reduce the number of animals used in routine toxicity testing, by identifying chemicals with high neurotoxic potential.


1992 ◽  
Vol 45 (11) ◽  
pp. 1845 ◽  
Author(s):  
GB Barlin ◽  
FL Tian ◽  
B Kotecka ◽  
KH Rieckmann

Twenty-four mono-Mannich bases of the general formulae 4'-chloro-3-[7″-chloro(and trifluoro-methyl)quinolin-4'-yl]amino-5-(substituted amino)methylbiphenyl-4-ols and 4'-bromo(and 3'- trifluoromethyl-3(substituted amino)methyl-5(7″-trifluoromethylquinolin-4″-yl) aminobiphenyl-2-ols have been prepared by condensation of the 4-chloro heterocycle with 5-amino-3-(N-substituted amino)methyl-4'-chlorobiphenyl-4-ols or 5-amino-3-(N-substituted amino)methyl- 4'-bromo(or 3'-trifluoromethyl)biphenyl-2-ols. The antimalarial activity of these products in in vitro tests against Plasmodium falciparum reveals many with IC50 values of 50-100 nM ( chloroquine 20-40 nM ). The biphenyl-2-ols were more active than comparable biphenyl-4-ols.


2016 ◽  
Vol 87 (17) ◽  
pp. 2117-2126 ◽  
Author(s):  
Małgorzata Cieślak ◽  
Agnieszka Karaszewska ◽  
Ewa Gromadzińska ◽  
Izabela Jasińska ◽  
Irena Kamińska

The article presents the results of measurements of pressure exerted by two model knitted products – bands with different structure (WI jersey weft-knitted fabric and WII openwork warp-knitted fabric). The tests were carried out with using the I-Scan system (in vivo and in vitro tests) and the STM 579 device (in vitro test). A comparative analysis of the in vivo and in vitro results for the I-Scan method and in vitro results for the I-Scan and STM 579 method was performed. It was found that the pressure values are lower for openwork warp-knitted fabric than for jersey weft-knitted fabric both in the case of the in vitro and in vivo tests, and the values of pressure for the same band are higher in the case of the in vitro tests.


1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 19-22
Author(s):  
Marcel B. Roberfroid ◽  
Fabienne Goethals

Foreword — Animal experimentation is an emotional topic, which arouses passionate feelings both in animal protection groups and in the scientific community. For many years, antivivisectionists have fought for the abolition of all animal experimentation, whereas other groups campaign for suppression/reduction of the level of pain animals suffer because of experimentation. Despite all these efforts, the number of animals used in scientific research does not seem to have decreased significantly during the last few years. At best, this number remains constant or shows minor reductions in some countries, whereas in others it is still increasing. In addition to this situation, which certainly does not satisfy the antivivisectionists, the validity of the use of animal models in biomedical research is increasingly being questioned. On the other hand, a number of developments and projects exist which attest to the growing interest of scientists in in vitro models which use few, or even no, animals. Such a change in attitude is particularly evident in practice and research in toxicology, which uses a large number of animals. Taking into account the special status of toxicology among the biomedical sciences, since its practice is required and defined by laws and directives, a semantic problem exists over which adjective should be applied to describe such new methods. For some, it must be alternative — for consistancy to underline the possibility of replacing classical in vivo tests with new in vitro tests, the validity of which is demonstrated by reference to these in vivo tests. For others, it has to be complementary — to characterise the new protocols and the new experimental models which are of interest, because they contribute to the improvement of toxicology by strengthening its scientific nature. For a third group, it must be adjunct — to emphasise the relatively minor role of non-animal tests in relation to the conventional animal tests. It is the second concept that is favoured in this article. The experimental models to which it applies will, according to the Three Rs of Russell & Burch (1), lead either to the replacement of animal models, or to a reduction in the number of animals used or to refinement of test procedures in order to minimise the suffering and stress caused to animals.


ChemInform ◽  
2006 ◽  
Vol 37 (32) ◽  
Author(s):  
Ange-Desire Yapi ◽  
Alexis Valentin ◽  
Jean-Michel Chezal ◽  
Olivier Chavignon ◽  
Bernard Chaillot ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2488
Author(s):  
Judith Salas-Oropeza ◽  
Manuel Jimenez-Estrada ◽  
Armando Perez-Torres ◽  
Andres Eliu Castell-Rodriguez ◽  
Rodolfo Becerril-Millan ◽  
...  

Bursera morelensis is used in Mexican folk medicine to treat wounds on the skin. Recently, it was shown that the essential oil (EO) of B. morelensis has wound healing activity, accelerating cutaneous wound closure and generating scars with good tensile strength. α-pinene (PIN) and α-phellandrene (FEL) are terpenes that have been found in this EO, and it has been shown in different studies that both have anti-inflammatory activity. The aim of this study was to determine the wound healing activity of these two terpenes. The results of in vitro tests demonstrate that PIN and FEL are not cytotoxic at low concentrations and that they do not stimulate fibroblast cell proliferation. In vivo tests showed that the terpenes produce stress-resistant scars and accelerate wound contraction, due to collagen deposition from the early stages, in wounds treated with both terpenes. Therefore, we conclude that both α-pinene and α-phellandrene promote the healing process; this confirms the healing activity of the EO of B. morelensis, since having these terpenes as part of its chemical composition explains part of its demonstrated activity.


1958 ◽  
Vol 107 (5) ◽  
pp. 711-729 ◽  
Author(s):  
N. Raphael Shulman

Regulated intravenous doses of quinidine were given to patients with the antibody of quinidine purpura to produce controlled thrombocytopenia without clinical sequelae. The degree of thrombocytopenia and the rate at which it developed were dependent on the relative plasma concentration of quinidine and antibody. By relating in vivo changes in platelet levels to concurrent in vitro tests for antibody activity and to quantitative relationships between reactants determined in Papers I and III of this series, it was concluded that the amount of antibody which attaches to platelets when thrombocytopenia develops is insufficient to cause complement fixation or platelet agglutination. Platelets do not appear to be destroyed directly by reaction with antibody in vivo. The minimal amount of antibody which does attach to platelets in vivo appears to increase their susceptibility to the usual mechanisms of sequestration. Megakaryocytes and blood vessels do not appear to be affected directly by the antibody which causes quinidine purpura, and hemorrhagic manifestations of the disease appear to be consequent to changes in platelets alone. A safe method of performing in vivo tests for the presence of an antibody of drug purpura is described. The implications of the present work in idiopathic thrombocytopenic purpura are discussed.


2010 ◽  
Vol 20 (9) ◽  
pp. 1523-1529 ◽  
Author(s):  
Bhupendra Singh ◽  
Dipak Chetia ◽  
S. K. Puri ◽  
Kumkum Srivastava ◽  
Anil Prakash

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