Home About us Contact
|
Home About us Contact | ||
|
|
||
In-vitro Activity (in-vitro + activity)
Selected AbstractsSynthesis and In-vitro Activity of 4,-Modified Analogues of ddA as Potent Anti-HIV AgentsARCHIV DER PHARMAZIE, Issue 10 2009Joon Hee Hong Abstract This paper reports the synthesis of novel 4,-hydrophobic pocket deoxythreosyl C-nucleosides. The key threose-like intermediates 9 and 14 were constructed from acyclic ketone derivatives, respectively. The antiviral activities of the synthesized compounds against the HIV-1, HSV-1, HSV-2, and HCMV viruses were evaluated. The 9-deaza-adenine derivatives 10 and 20 showed good anti-HIV activity without exhibiting significant cytotoxicity. [source] In-vitro activity and in-vivo efficacy of catheters impregnated with chloroxylenol and thymol against uropathogensCLINICAL MICROBIOLOGY AND INFECTION, Issue 2 2008M. D. Mansouri No abstract is available for this article. [source] Anti-plasmodial and anti-leishmanial activity of conformationally restricted pentamidine congenersJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2006Tien L. Huang A library of 52 pentamidine congeners in which the flexible pentyldioxy linker in pentamidine was replaced with various restricted linkers was tested for in-vitro activity against two Plasmodium falciparum strains and Leishmania donovani. The tested compounds were generally more effective against P. falciparum than L. donovani. The most active compounds against the chloroquine-sensitive (D6, Sierra Leone) and -resistant (W2, Indochina) strains of P. falciparum were bisbenzamidines linked with a 1,4-piperazinediyl or 1, 4-homopiperazinediyl moiety, with IC50 values (50% inhibitory concentration, inhibiting parasite growth by 50% in relation to drug-free control) as low as 7 nM based on the parasite lactate dehydrogenase assay. Seven piperazine-linked bisbenzamidines substituted at the amidinium nitrogens with a linear alkyl group of 3,6 carbons (22, 25, 27, 31) or cycloalkyl group of 4, 6 or 7 carbons (26, 32, 34) were more potent (IC50 < 40 nM) than chloroquine or pentamidine as anti-plasmodial agents. The most active anti-leishmanial agents were 4,4,-[1,4-phenylenebis(methyleneoxy)]bisbenzenecarboximidamide (2, IC50 , 0.290 ,M) and 1,4-bis[4-(1H-benzimidazol-2-yl)phenyl] piperazine (44, IC50,0.410 ,M), which were 10- and 7-fold more potent than pentamidine (IC50 , 2.90 ,M). Several of the more active anti-plasmodial agents (e.g. 2,31, 33, 36,38) were also potent anti-leishmanial agents, indicating broad antiprotozoal properties. However, a number of analogues that showed potent anti-plasmodial activity (1, 18, 21, 22, 25,28, 32, 43, 45) were not significantly active against the Leishmania parasite. This indicates differential modes of anti-plasmodial and anti-leishmanial actions for this class of compounds. These compounds provide important structure-activity relationship data for the design of improved chemotherapeutic agents against parasitic infections. [source] Design, Synthesis, and Antifungal Activity of Novel Conformationally Restricted Triazole DerivativesARCHIV DER PHARMAZIE, Issue 12 2009Wenya Wang Abstract A series of new triazole derivatives were designed and synthesized on the basis of the active site of lanosterol 14,-demethylase from Candida albicans (CACYP51). 2-(2,4-Difluorophenyl)-3-(methyl-(3-phenoxyalkyl)amino)-1-(1H -1,2,4-triazol-1-yl)propan-2-ols show excellent in-vitro activity against most of the tested pathogenic fungi. The MIC80 value of compound 8a against Candida albicans is 0.01 ,M, which provides a good starting template for further structural optimization. The binding modes of the designed compounds were investigated by flexible molecular docking. The compounds interacted with CACYP51 through hydrophobic, van-der-Waals, and hydrogen-bonding interactions. [source] Nitric Oxide Synthase Inhibition by Pentacycloundecane Conjugates of Aminoguanidine and TryptamineARCHIV DER PHARMAZIE, Issue 2 2009Dennis K. Wilkes Abstract This paper describes the synthesis and in-vitro activity of pentacycloundecane-conjugated aminoguanidine and tryptamine analogues on nitric oxide synthase (NOS) using rat brain homogenate. Both aminoguanidine and tryptamine-derived NOS inhibitors show selectivity towards the inducible and neuronal isoforms of the NOS enzyme, but are weak inhibitors and complete inhibition of the enzyme occurs only at high millimolar concentrations. In view of the increased NOS inactivation observed with alkyl substitution of these structures, the present study aimed to evaluate the effect of the pentacycloundecane cage moiety as an alkyl substituent on the in vitro NOS inhibition of aminoguanidine and tryptamine compounds. Comparison of the IC50 values of aminoguanidine (IC50 = 2.306×10,3 M) and 8-imino- N -guanidino-pentacyclo-undecane 2 (IC50 = 8.803×10,5 M) revealed a more than 26-fold increase in potency. The ability of tryptamine to inhibit NOS activity was also markedly improved by the various pentacycloundecane substituents. The compounds, 3-hydroxy-4-[3-(2-aminoethyl)indole]-azahexacyclo[5.4.1.02,6.03,10.05,9.08,11]dodecane 4 and 8-[3-(2-aminoethyl) indole]-pentacyclo[5.4.02,6.03,10.05,9]undecane 7 showed the best activity of the tryptamine analogues with a more than 3-fold increase in nitric oxide synthase inhibition. The results confirmed that the pentacycloundecane structure substantially enhanced the NOS inhibitory potency as observed for the six new NOS inhibitors. [source] Synthesis and In-Vitro Cytotoxicity Evaluation of Novel Naphtindolizinedione Derivatives, Part II: Improved Activity for Aza-AnaloguesARCHIV DER PHARMAZIE, Issue 2 2009Andrea Defant Abstract Our previous investigation on potential antitumor agents now got enriched by the evaluation of in-vitro activity against a full panel of NCI cancer cell lines for five new compounds. The concurrent presence in the molecular structure of a nitrogen atom in the aromatic system and a N,N -dimethylaminoethyl amide chain play a decisive role to enhance cytotoxicity. The N,N -anti compound 14 shows a higher activity than its N,N -syn isomer, exhibiting the best selective inhibition against the melanoma MALME-3M cell line, with a GI50 -value (= 30 nM) corresponding to a 330-fold increase in activity compared to the corresponding deaza-analogue. Compound 14 is efficiently synthesized by aminolysis of the ester obtained as a single regio-isomer by an one-pot three-component procedure involving metal-assisted cyclization under microwave irradiation conditions. [source] | ||||||||||