In Search of Novel Agents for Therapy of Tropical Diseases and Human Immunodeficiency Virus

Abstract

Malaria, sleeping sickness, Chagas' disease, Aleppo boil, and AIDS are among the tropical diseases causing millions of infections and cases of deaths per year because only inefficient chemotherapy is available. Since the targeting of the enzymes of the polyamine pathway may provide novel therapy options, we aimed to inhibit the deoxyhypusine hydroxylase, which is an important step in the biosynthesis of the eukaryotic initiation factor 5A. In order to identify new lead compounds, piperidines were produced and biologically evaluated. The 3,5-diethyl piperidone-3,5-dicarboxylates 11 and 13 substituted with 4-nitrophenyl rings in the 2 and 6 positions were found to be active against Trypanosoma brucei brucei and Plasmodium falciparum combined with low cytotoxicity against macrophages. The corresponding monocarboxylates are only highly active against the T. brucei brucei. The piperidine oximether 53 demonstrated the highest plasmodicidal activity. Moreover, compounds 11 and 53 were also able to inhibit replication of HIV-1.

Inhibition of prolyl oligopeptidase with a synthetic unnatural dipeptide

“…Attempted protection of the aldehyde as an acetal failed to provide any protected product. 10,11 At this point a different route was required. The alcohol of 5 was protected with a TBDMS group to give silyl ether 6.…”

Synthesis and biological evaluation of some novel tetrahydroquinolines as anticancer and antimicrobial agents

“…Twenty-one analogs (1,4,5,7,8,11,12,15,16,24,25,28,30,33,39,40,42,45,46, 48 and 49) were selected to be evaluated for their in vitro cytotoxic effect via the standard MTT method against a panel of three human tumor cell lines: Caucasian breast adenocarcinoma MCF7, hepatocellular carcinoma HepG2 and colon carcinoma HT29. The results of LC 50 (mM), which is the Figure 1.…”

“…Among the wide variety of heterocycles that have been explored for developing pharmaceutically important molecules, pyridines and fused pyridine ring systems have received much attention since they are proved to be biologically versatile compounds possessing a variety of activities. A wide range of chemotherapeutic activities have been ascribed to pyridine derivatives including antimicrobial [1][2][3] , antiamoebic 1 , antiparasitic 4 and antiviral 5,6 activities. As far as the antineoplastic potential is concerned, pyridine derivatives were reported to contribute to a variety of anticancer activity including cytotoxic 7,8 , antiproliferative 9 and CDK kinase inhibitory activity 10 .…”

Synthesis and characterization of a novel series of benzenesulfonylurea and thiourea derivatives of 2H-pyran and 2H-pyridine-2-ones as antibacterial, antimycobacterial and antifungal agents

“…On the other hand, a broad spectrum of pharmacological properties has been ascribed to the structurally-relevant 2-pyridone derivatives. In addition to their pronounced effects on the cardiovascular system as cardiotonic [13,14], calcium channel blocking [15] and tissue factor VII inhibitory agents [16], some pyridones were reported to exhibit potential antimicrobial [17][18][19][20], antitubercular [21,22], antiamoebic [23], antiparasitic [24], antimalarial [25], antifungal and antiviral [26][27][28] activities.…”