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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During development of nitroheterocycles with potential antimycobacterial activities we have tested against Mycobacterium tuberculosis a number of pyrroles strictly related to pyrrolnitrin, an antifungal antibiotic isolated from Streptomyces pyrrocinia. Some of the tested arylpyrrole derivatives and pyrrolnitrin have shown appreciable inhibiting activity against M. tuberculosis and M. avium. SAR studies well correlate antimycobacterial potency with the presence of halogens in the phenyl ring and a nitro group at position 3 of pyrrole.
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PMID:Pyrrolnitrin and related pyrroles endowed with antibacterial activities against Mycobacterium tuberculosis. 987 50

The effects of acute exposure to GSM-900 microwaves (900 MHz, 217 Hz pulse modulation) on the clinical parameters of the acute experimental allergic encephalomyelitis (EAE) model in rats were investigated in two independent experiments: rats were either habituated or nonhabituated to the exposure restrainers. EAE was induced with a mixture of myelin basic protein and Mycobacterium tuberculosis. Female Lewis rats were divided into cage control, sham exposed, and two groups exposed either at 1.5 or 6.0 W/kg local specific absorption rate (SAR averaged over the brain) using a loop antenna placed over their heads. There was no effect of a 21 day exposure (2 h/day) on the onset, duration, and termination of the EAE crisis.
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PMID:Effects of GSM-900 microwaves on the experimental allergic encephalomyelitis (EAE) rat model of multiple sclerosis. 1266 5

Homolytic aroylation of pyrazine nucleus with various substituted aromatic carbaldehydes afforded a series of 5-aroylpyrazine-2-carboxylic acid derivatives. The synthetic approach, analytical and spectroscopic data of all compounds synthesized, their preliminary in vitro evaluation of antituberculotic and antifungal activities, cytotoxicity data and subsequent SAR studies are presented. Among all derivatives prepared, only 5-(4-chlorobenzoyl)-pyrazine-2-carbothioamide (3d) showed promising activity (90% inhibition) against Mycobacterium tuberculosis. The highest antifungal effect (MIC<1.95 microM ml(-1)) against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 5-benzoylpyrazine-2-carbothioamide (3a). Thioamides exhibited higher in vitro antimicrobial activity than the corresponding amides.
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PMID:Substituted 5-aroylpyrazine-2-carboxylic acid derivatives: synthesis and biological activity. 1457 61

The marine sponge constituent aaptamine (1) has been converted to the cancer cell growth inhibitor and antibiotic designated hystatin 2 (8a). Herein, we also report results of an initial SAR evaluation of new benzyl derivatives of aaptamine (1). Single benzylation was found to occur at nitrogen N-4 and led to the formation of the 4-benzylaaptamine derivatives 7a-c, whereas double benzylation gave the quaternary 1H-benzo[de][1,6]-naphthyridinium salts 8a-c. The anticancer and antimicrobial properties of these aaptamine derivatives are described. The quaternary ammonium salts 8a (hystatin 2) and 8b exhibited significant inhibitory activity against the murine P388 lymphocytic leukemia and a minipanel of human cancer cell lines. Salts 8a and 8b also had broad spectrum antimicrobial activities and were most potent against Mycobacterium tuberculosis, Neisseria gonorrhoeae, and Micrococcus luteus. Naphthyridinium chloride 8a was selected for further development, and results of an initial cell cycle analysis and a cDNA microarray study showed effects consistent with inhibition of the S-phase of cell growth.
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PMID:Antineoplastic agents. 499. Synthesis of hystatin 2 and related 1H-benzo[de][1,6]-naphthyridinium salts from aaptamine. 1502 69

A novel series of 3-morpholino rifamycins in which the C25 acetate group was replaced by a carbamate group were prepared and found to exhibit significantly improved antimicrobial activity than rifampin against Mycobacterium smegmatis. Further characterization of such compounds suggests that relatively large groups attached to the rifamycin core via a C25 carbamate linkage prevent inactivation via ribosylation of the C23 alcohol as catalyzed by the endogenous rifampin ADP-ribosyl transferase of M. smegmatis. SAR studies of the C25 carbamate rifamycin series against M. smegmatis and other bacteria are reported.
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PMID:New C25 carbamate rifamycin derivatives are resistant to inactivation by ADP-ribosyl transferases. 1707 48

A series of cyclic sulfones has been synthesized and their activity against beta-ketoacyl-ACP-synthase III (FabH) has been investigated. The compounds are selectively active against Escherichia coli FabH (ecFabH), but not Mycobacterium tuberculosis FabH (mtFabH) or Plasmodium falciparum KASIII (PfKASIII). The activity against ecFabH ranges from 0.9 to >100microM and follows a consistent general SAR trend. Many of the compounds were shown to have antimalarial activity against chloroquine (CQ)-sensitive (D6) P. falciparum (IC(50)=5.3microM for the most potent inhibitor) and some were active against E. coli (MIC=6.6microg/ml for the most potent inhibitor).
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PMID:Synthesis and biological evaluation of thiazolidine-2-one 1,1-dioxide as inhibitors of Escherichia coli beta-ketoacyl-ACP-synthase III (FabH). 1718 94

A series of N(1)-(4-substituted-benzyl)-pyrimidines were synthesized as potential inhibitors of thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt). Key SAR parameters included the chain length substitution in para position of the benzyl ring, the functional group terminating the alkyl chain, and the substituent on the C-5 pyrimidine ring. Synthesized molecules were assayed against both recombinant enzyme and mycobacteria cultures. The most potent compounds have K(i) values in the micromolar range and an MIC(50) of 50microg/mL against Mycobacterium bovis. These results will guide the design of a new generation of lead compounds.
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PMID:Substituted benzyl-pyrimidines targeting thymidine monophosphate kinase of Mycobacterium tuberculosis: synthesis and in vitro anti-mycobacterial activity. 1846 7

The present study explores the variability of biological responses from the perspective of sample purity and introduces the concept of purity-activity relationships (PARs) in natural product research. The abundant plant triterpene ursolic acid (1) was selected as an exemplary natural product due to the overwhelming number yet inconsistent nature of its approximate 120 reported biological activities, which include anti-TB potential. Nine different samples of ursolic acid with purity certifications were obtained, and their purity was independently assessed by means of quantitative 1H NMR (qHNMR). Biological evaluation consisted of determining MICs against two strains of virulent Mycobacterium tuberculosis and IC50 values in Vero cells. Ab initio structure elucidation provided unequivocal structural confirmation and included an extensive 1H NMR spin system analysis, determination of nearly all J couplings and the complete NOE pattern, and led to the revision of earlier reports. As a net result, a sigmoid PAR profile of 1 was obtained, demonstrating the inverse correlation of purity and anti-TB bioactivity. The results imply that synergistic effects of 1 and its varying impurities are the likely cause of previously reported antimycobacterial potential. Generating PARs is a powerful extension of the routinely performed quantitative correlation of structure and activity ([Q]SAR). Advanced by the use of primary analytical methods such as qHNMR, PARs enable the elucidation of cases like 1 when increasing purity voids biological activity. This underlines the potential of PARs as a tool in drug discovery and synergy research and accentuates the need to routinely combine biological testing with purity assessment.
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PMID:Purity-activity relationships of natural products: the case of anti-TB active ursolic acid. 1879 82

A series of analogs of 2-tosylnaphthalene-1,4-diol were prepared and were found to be potent 10-20 nM reversible inhibitors of the Escherichia coli FabH enzyme. The inhibitors were also effective but to a lesser degree (30 nM-5 microM), against the Mycobacterium tuberculosis and Plasmodium falciparum FabH enzymes. Preliminary SAR studies demonstrated that the sulfonyl group and naphthalene-1,4 diol were required for activity against all enzymes but the toluene portion could be significantly altered and leads to either modest increases or decreases in activity against the three enzymes. The in vitro activity of the analogs against E. coli FabH parallel the in vivo activity against E. coli TolC strain and many of the compounds were also shown to have antimalarial activity against P. falciparum.
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PMID:Synthesis and biological evaluation of novel sulfonyl-naphthalene-1,4-diols as FabH inhibitors. 1899 91

Tuberculosis is a leading infectious cause of death worldwide. Because of the concern of the resistance to most of the commonly used drugs displayed by the considered mycobacteria, most efforts have been done to introduce new anti-tubercular agents. Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant anti-tubercular activity. In this study, we synthesized new derivatives of 1,4-dihydropyridines in which different alkyl and aryl esters and diethyl carbamoyl are substituted in C-3 and C-5 of the DHP ring. In addition nitroimidazole ring is substitutes at C-4 position. These asymmetric analogues were synthesized by a modified Hantzsh reaction using procedure reported by Meyer. The in vitro anti-tubercular activity of compounds against Mycobacterium tuberculosis was evaluated. The results indicate that the compounds containing aromatic esters are more potent than alkyl ones. The most potent aromatic compound (R=3-phenylpropyl) exhibits comparable anti-tubercular activity (MIC=1 micromol/ml) with reference compound isoniazide (INH) (MIC=1 micromol/ml). Conformational analysis, SAR studies of these compounds showed that increasing in lipophilicity and rotable bonds of these compounds resulted in increasing anti-tubercular activity.
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PMID:Synthesis and biological evaluation of some new 1,4-dihydropyridines containing different ester substitute and diethyl carbamoyl group as anti-tubercular agents. 1916 89


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