Antimicrobial agents

Among 15 antimycotic agents tested, maximum activity was displayed by 5,7-dichloro-8-oxyquinoline, both as regards the microorganism spectrum and the minimum inhibitory concentration. The antimycotic effect of 2-aminotridecane-undecylenate and 2-aminotridecane-2-chloro-4-nitrophenolate was greater than that of 2-aminotridecane, undecylenic acid and 2-chloro-4-nitrophenol alone. Biochemical resistance develops relatively rapidly in aTrichophyton mentagrophytes strain on contact with fungicidin, 2-chloro-4-nitrophenol and 5,7-dichloro-8-oxyquinoline. ATrichophyton mentagrophytes strain resistant to one of these three agents is also several times less sensitive to all the other test substances except septonex.     

Antiangiogenic agents

Comment on: Conley SJ, et al. Proc Natl Acad Sci USA 2012; In press     

Antimicrobial agents

The development of acquired, temporary resistance induced by an adaptation mechanism as a result of direct contact of the cell with an antimycotic, was demonstrated in pathogenic species of the genusCandida. Acquired resistance induced by one substance was manifested in multiresistance to other, structurally quite different, antimycotics. Cultivation of the strain on antimycotic-free medium led to relatively rapid deadaptation and the strain regained its initial sensitivity. The sensitivity of adapted and deadapted strains was studied by the dilution method (determining MIC values) and by the “direct” Warburg method (evaluating metabolic quotients).     

Antimicrobial agents

In a study of the effect of progesterone, its hydroxy derivatives and various sterols on the growth of dermatophytes, it was demonstrated that all the steroid compounds employed inhibited growth of the 51 strains of dermatophytes tested. No significant differences were found in sensitivity to the given steroids, either in dermatophyte strains of the same species, but of different origin, ior in different species of the four genera used (Trichophyton, Microsporum, Epidermophyton andKeratinomyces). Hydroxylation of the progesterone molecule in any except the C-21 position lowered the inhibitory effect. The course of the transformation reaction on the progesterone or cholesterol molecule was likewise of a uniform character from the aspect of species specificity. Progesterone was simultaneously hydroxylated in positions 15α and 15β by all the strains, giving rise to monohydroxy-derivatives as the main metabolites, and cholesterol was oxidized to cholestenone.     

Triglyceride-lowering agents

This review is the first attempt at systematization of the literature data on the structures and activities of triglyceride-lowering agents which used in medical practice or are in development. The effects and mechanisms of action of statins, squalene synthase inhibitors, fibrates, PPARα and PPARα/γ agonists, nicotinic acid, omega-3 fatty acids and some other molecular targets were considered. Unfortunately, to date, harmless and effective triglyceride-lowering drug still does not exist and there is still need for development of better triglyceride-lowering agents.     

Detecting agents

This paper reviews a recent set of behavioural studies that examine the scope and nature of the representational system underlying theory-of-mind development. Studies with typically developing infants, adults and children with autism all converge on the claim that there is a specialized input system that uses not only morphological cues, but also behavioural cues to categorize novel objects as agents. Evidence is reviewed in which 12- to 15-month-old infants treat certain non-human objects as if they have perceptual/attentional abilities, communicative abilities and goal-directed behaviour. They will follow the attentional orientation of an amorphously shaped novel object if it interacts contingently with them or with another person. They also seem to use a novel object's environmentally directed behaviour to determine its perceptual/attentional orientation and object-oriented goals. Results from adults and children with autism are strikingly similar, despite adults' contradictory beliefs about the objects in question and the failure of children with autism to ultimately develop more advanced theory-of-mind reasoning. The implications for a general theory-of-mind development are discussed.     

Antimicrobial agents

In the microbial degradation of Fungicidin by lower pathogenic fungi, no significant differences were found in the rate of its degradation by the various species of dermatophytes employed (Trichophyton mentagrophytes, Trichophyton rubrum andMicrosporum gypseum), but there was a marked difference in the rate of enzymatic degradation by microorganisms adapted and not adapted to Fungicidin or Amphotericin B. After four hours' degradation of Fungicidin by non-adapted strains, about 70% of the Fungicidin in the medium was still intact, whereas it was completely degraded by adapted strains during the same interval. The addition of protein biosynthesis inhibitors (chloramphenicol and tetracycline) and of the antifungally active substance 2-aminotridecane did not influence the microbial degradation of Fungicidin by dermatophytes.     

Golgi-disturbing agents

 Pharmacological agents have proven useful for gaining fundamental insights into the biology of the Golgi apparatus. This review summarizes pertinent and recent work on the effects on this organelle of monensin, brefeldin A, bafilomycin, ilimaquinone, okadaic acid, retinoic acid, and nocodazole. The molecular targets of monensin, brefeldin A, ilimaquinone, and retinoic acid remain to be elucidated whereas those for bafilomycin (vacuolar H⁺-ATPase), okadaic acid (serine/threonine phosphatases types 1, 2a, and 2b), and nocodazole (microtubules) are reasonably well understood. The molecular target of brefeldin has not been defined, but has been suggested to involve guanine nucleotide exchange proteins acting on ADP-ribosylation factor 1. Whether a defined molecular target can be found for monensin must be questioned since its main action consists in exchanging protons for Na⁺ which leads to osmotic swelling of post-Golgi endosomal structures and Golgi subcompartments by virtue of its membrane-associated effect as a cationophore. Brefeldin A was one of the most thoroughly investigated Golgi-disturbing agents and proved instrumental in unraveling retrograde flow mechanisms in the secretory pathways. Okadaic acid attracted interest for its properties mimicking mitotic fragmentation of the Golgi apparatus. Nocodazole was instrumental in establishing the cytoskeletal anchoring of the Golgi apparatus close to the microtubular organizing center. Accepted: 29 September 1997     

Antimicrobial agents

The effect of 2-aminotridecane and its addition salts with different substituted phenols on growth ofCandida albicans was studied and the fungistatic and fungicidal activity of these substances was compared. The addition 2-aminotridecane salts with 2,4,5-trichlorophenol and with 2-chloro-4-introphenol were found to be the most active in all three tests. The activity of the other addition salts tested differed little from that of actual 2-aminotridecane.     

Antimicrobial agents

The antimicrobial effectivity of 32 derivatives and analogues of 10-(4-methylpiperazino)-10,11-dihydrodibenzo(b,f)thiepine was investigated and it was found that substituents in rings A and C and in the piperazine residue affect the antimicrobial potency of the compound. The derivative with the chlorine atom in position 3 was found to be most active in suppressing microbial growth. Substitution with chlorine of the ring C in positions 6, 7 and 8 produced derivatives with highest tuberculostatic activity. The growth of Gram-negative microorganisms (with the exception ofKlebsiella pneumoniae), as well as of fungiTrichophyton mentagrophytes, Candida albicans andAspergillus niger, was not suppressed by any of the derivatives. The antimicrobial effect of the active derivatives was demonstrated on strains ofStreptococcus haemolyticus, Staphylococcus pyogenes aureus, Mycobacterium tuberculosis, Klebsiella pneumoniae andSaccharomyces pastorianus.     

Antiangiogenic agents

A greater understanding of the complex process of tumor-induced angiogenesis, coupled with the notion that tumors require a blood supply to both grow and metastasize, has fueled the search for agents that block or disrupt the angiogenic process. Because normal vascular endothelial cells (ECs) turn over so slowly, conventional wisdom suggests that an antiangiogenic approach to cancer therapy should offer improved efficacy and reduced toxicity, without the potential for drug resistance. Numerous reports have identified small molecules or antibodies that can interfere with one or more key steps in EC signaling, migration or differentiation. Three new compounds, ZD4190, SU6668 and PD 0173073, have been reported during the past year to have significant and selective antiangiogenic activity, as well as antitumor activity.