The use of long acting sulfonamides, alone or with pyrimethamine, in malaria (with special reference to sulformetoxine)

Review of the early literature as well as more recent results show that sulfonamides possess a distinct antimalarial activity. However, when give alone, their action is less marked and slower than that of the antimalarials commonly used in the treatment of the acute attack. Combinations with pyrimethamine provide better results, even in cases of pyrimethamine and chloroquine resistance. This warrants further investigations in an attempt to develop a therapeutic agent suitable for the treatment of such resistant cases. It may also be possible with an appropriate combination of pyrimethamine with a sulfonamide to achieve a satisfactory method for suppressive treatment both in areas with and without pyrimethamine resistance. Three main points must still be carefully studied: 1) the risk of developing malaria resistance against one or both of the components of the combination. 2) The risk of developing bacterial resistance to sulfonamides if these substances are used on a large scale in too low doses. It seems indeed that antimalarial effect with the combination of sufonamides + pyrimethamine can be obtained with doses of sulfonamides which are below those usually employed in bacterial diseases. Since the range of the ratios providing potentiation is rather large, only ratios of the combination sulfonamides: pyrimethamine should be chosen in which an antfbacterial sulfonamidemia is guaranteed. 3) It goes without sayinq that, although both pyrimethamine and modem sulfonamides, when given by themselves, have proved tc possess a large margin of safety, long term administration of their combination should be careful studied from the point of view of possible side effects. Substantial evidence has already been produced to show that the long acting sulfonamide Fanasil (Ro 4-4393) given once or once weekly possesses marked schizonticidal activity against P. falciparum. Although its action is slower than that of 4-aminoquinolines, it may be useful as a second choice drug in semi-immune subjects for the therapy of falciparum malaria. Preliminary results show that, when combined with pyrimethamine, Fanasil is highly effective in suppressing fever and asexual parasitemia due to P. falciparum. Single doses of 1 g Fanasil together with 50 mg pyrimethamine seem to be adequate for the treatment of acute falciparum malaria in semi-immune patients. The onset of action of the combination is much more rapid than that of the single components. Weekly doses of 500 mg Fanasil and 25 mg pyrimeihamine appear to provide satisfactory suppressive effects against P. falciparum at least in East Africa. This combination is active on strains which do not respond satisfactorily to the standard doses of pyrimethamine and/or chloroquine and seems to have a satisfactory sporontocidal effect. Preliminary results indicate that Fanasil alone cannot be recommended for use against the other human malaria parasites. The combination with pyrimethamine appears to be much more effective. East African strains of P. malariae seem to respond better to the combination than do Malayan strains of P. vivax but further trials are required before definite assessment can be made. Fanasil by itself has no gametocytoddal or sporontocidal action but seems to potentiate the effect of pyrimethamine at least on sporogony of P. falciparum.

Bis-sulfonamides quirals amb simetria C2 com a possibles organocatalitzadors per a l'addició estereoselectiva de nucleòfils a cations N-acilimini

En aquest treball s’ha plantejat estudiar la capacitat de diferents bissulfonamides per promoure, actuant com a àcids Brønsted, l’addició estereoselectiva d’un grup al·lil o un indole a un catió acilimini. Per això, s’han sintetitzat diversos tipus de bis-sulfonamides amb simetria C2, en forma enantiopura, i preparat precursors genèrics de cations N-acilimini. S’han dut a terme reaccions d’al·lilació i d’addició d’indole en diferents condicions i amb les diferents sulfonamides. Es va estudiar la possible estereoselectivitat dels productes d’addició, però en cap cas la presència de les bis-sulfonamides sintetitzades en la reacció ha afectat a l’estereoselectivitat de les addicions.

Synthesis, structure and physicochemical properties of zinc and copper complexes based on sulfonamides containing 8-aminoquinoline ligands

Sulfonamides obtained by reaction of 8-aminoquinoline with 4-nitrobenzenesulfonylchloride and 2,4,6-triisopropylbenzenesulfonyl chloride were used to synthesize coordination compounds with CuII and ZnII with a ML2 composition. Determination of the crystal structures of the resulting zinc and copper complexes by X-ray diffraction show a distorted tetrahedral environment for the [Cu(qnbsa)2], [Cu(qibsa)2] and [Zn(qibsa)2] complexes in which the sulfonamide group acts as a bidentate ligand through the nitrogen atoms from the sulfonamidate and quinoline groups. The complex [Zn(qnbsa)2] crystallizes with a water molecule from the solvent and the Zn is five-coordinated and shows a bipyramidal-trigonal geometry. The electrochemical and electronic spectroscopy properties of the copper complexes are also discussed.

Stability constants and thermodynamic parameters of cadmium complexes with sulfonamides and cephapirin

Stability constant (log beta) and thermodynamic parameters of Cd2+ complexes with sulfonamide and cephapirin were determined by Polarographic technique at pH = 7.30 ± 0.01 and µ = 1.0 M KNO3 at 250°C. The sulfonamides were sulfadiazine, sulfisoxazole, sulfamethaxazole, sulfamethazine, sulfathiazole, sulfacetamide and sulfanilamide used as primary ligands and cephapirin as secondary ligand. Cd2+ formed 1:1:1, 1:2:1 and 1:1:2 complexes. The nature of electrode processes were reversible and diffusion controlled. The stability constants and thermodynamic parameters (deltaG, deltaH and deltaS) were determined. The formation of the metal complexes has been found to be spontaneous, exothermic in nature, and entropically unfavourable at higher temperature.

Paracoccidioidomycosis: A comparative study of the evolutionary serologic, clinical and radiologic results for patients treated with ketoconazole or amphotericin B plus sulfonamides

A comparative study of two groups of patients with paracoccidioidomycosis was carried out with the objective of comparing the evolutionary serologic, clinical and radiologic results after 6, 12, 15 and 18 months of treatment with ketoconazole (22 patients) or amphotericin B plus sulfonamides (32 patients). The serologic data analyzed as a whole showed a tendency to sharper drops in antibody titers in the patients treated with ketoconazole. Clinically patients treated with ketoconazole fared better but the differences were not statistically significant. No statistical difference was detected between groups in terms of the results of radiologic evolution. © 1985 Martinus Nijhoff/Dr W. Junk Publishers.

A simple and rapid screening method for sulfonamides in honey using a flow injection system coupled to a liquid waveguide capillary cell

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Stimulation of human T cells with sulfonamides and sulfonamide metabolites

Exposure to sulfonamides is associated with a high incidence of hypersensitivity reactions. Antigen-specific T cells are involved in the pathogenesis; however, the nature of the antigen interacting with specific T-cell receptors is not fully defined.

Resolution of amino acids through the bromo-camphor sulfonamides.

Thesis (B.S.)--University of Illinois at Urbana-Champaign, 1921.

Sulfonamides in veterinary medicine,

Includes bibliography.

Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase

3-Fluoromethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines (14, 16, and 18-22) are highly potent and selective inhibitors of phenylethanolamine N-methyltransferase (PNMT). Molecular modeling studies with 3-fluoromethyl-7-(N-alkyl aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines, such as 16, suggested that the sulfonamide -NH-could form a hydrogen bond with the side chain of Lys57. However, SAR studies and analysis of the crystal structure of human PNMT (hPNMT) in complex with 7 indicated that the sulfonamide oxygens, and not the sulfonamide -NH-, formed favorable interactions with the enzyme. Thus, we hypothesized that replacement of the sulfonamide -NH-with a methylene group could result in compounds that would retain potency at PNMT and that would have increased lipophilicity, thus increasing the likelihood they will cross the blood brain barrier. A series of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines (23-30) were synthesized and evaluated for their PNMT inhibitory potency and affinity for the R2-adrenoceptor. A comparison of these compounds with their isosteric sulfonamides (14, 16, and 18-22) showed that the sulfones were more lipophilic but less potent than their corresponding sulfonamides. Sulfone 24 (hPNMT K-i = 1.3 mu M) is the most potent compound in this series and is quite selective for PNMT versus the R2-adrenoceptor, but 24 is less potent than the corresponding sulfonamide, 16 (hPNMT K-i = 0.13 mu M). We also report the crystal structure of hPNMT in complex with sulfonamide 15, from which a potential hydrogen bond acceptor within the hPNMT active site has been identified, the main chain carbonyl oxygen of Asn39. The interaction of this residue with the sulfonamide -NH-is likely responsible for much of the enhanced inhibitory potency of the sulfonamides versus the sulfones.

Sulfonyl-hydrazones of cyclic imides derivatives as potent inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase B (PtpB)

Searching lead compounds for new antituberculosis drugs, the activity of synthetic sulfonamides and sulfonyl-hydrazones were assayed for their potential inhibitory activity towards a protein tyrosine phosphatase from Mycobacterium tuberculosis - PtpB. Four sulfonyl-hydrazones N-phenylmaleimide derivatives were active (compounds 14, 15, 19 and 21), and the inhibition of PtpB was found to be competitive with respect to the substrate p-nitrophenyl phosphate. Structure-based molecular docking simulations were performed and indicated that the new inhibitor candidates showed similar binding modes, filling the hydrophobic pocket of the protein by the establishment of van der Waals contacts, thereby contributing significantly to the complex stability.

Multimedia fate modeling and comparative impact on freshwater ecosystems of pharmaceuticals from biosolids-amended soils

This study modeled the impact on freshwater ecosystems of pharmaceuticals detected in biosolids following application on agricultural soils. The detected sulfonamides and hydrochlorothiazide displayed comparatively moderate retention in solid matrices and, therefore, higher transfer fractions from biosolids to the freshwater compartment. However, the residence times of these pharmaceuticals in freshwater were estimated to be short due to abiotic degradation processes. The non-steroidal anti-inflammatory mefenamic acid had the highest environmental impact on aquatic ecosystems and warrants further investigation. The estimation of the solid-water partitioning coefficient was generally the most influential parameter of the probabilistic comparative impact assessment. These results and the modeling approach used in this study serve to prioritize pharmaceuticals in the research effort to assess the risks and the environmental impacts on aquatic biota of these emerging pollutants.

Delayed results of treatment of paracoccidioidomycosis with amphotericin B plus sulfamides versus amphotericin B alone

A delayed evaluation of two groups of patients with paracoccidioidomycosis was carried out. Both groups were treated with amphotericin B, "but one of them was submitted to maintenance treatment with sulfonamides. Statistical analysis showed that treatment is more effective when patients are maintained with sulfonamide drugs.