Inhibitory activity antibiotics

Wakusawa, S., Inoko, K., Miyamoto, K.-I., Kajita, S., Hasegawa, T, Harimaya, K., and Koyama, M. (1993) Staurosporine derivatives reverse multidrug resistance without correlation with their protein kinase inhibitory activities./. Antibiot., 46, 353-355. 

Many antibiotics have been found to have inhibitory activity on enzyme systems. This inhibition can be utilized as the basis of an assay system. 

Microbiologically based assay systems invariably measure the active antibiotic(s) or forms of the antibiotic that can be inhibitory to microorganisms. Immunological assays can measure both the active antibiotic as well as microbiologically inactive species. 

In 1993, Oki et al. isolated the novel carbazole antibiotics epocarbazolin A (258) and B (259) from the culture broth of Streptomyces anulatus T688-8 (230). They represent the first carbazole alkaloids with an epoxide moiety in a side chain, and are the epoxides corresponding to carbazomadurin A (256) and B (257). Epocarbazolin A (258) [oC + 75.0 (c 0.5, MeOH) and B (259) Mg -b 78.0 (c 0.5, MeOH) were obtained from Nature in optically active form. However, their absolute configuration is not known. These alkaloids showed potent 5-lipoxygenase inhibitory activity and weak antibacterial activity (230) (Scheme 2.63). 

Inhibitors of P-lactamase are known. The synthetic sulfone tazobactam (9.38), and clavulanic acid (9.39) both have weak antibacterial activity besides P-lactamase inhibitory activity, and they can be used in combination with vulnerable antibiotics. 

The risk of myopathy appears to be increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Lovastatin is metabolized by the CYP isoform 3A4. Certain drugs, that share this metabolic pathway can raise the plasma levels of lovastatin and may increase the risk of myopathy. These include cyclosporine, itraconazole, ketoconazole and other antifungal azoles, the macrolide antibiotics erythromycin and clarithromycin, HIV protease inhibitors, the antidepressant nefazodone, or large quantities of grapefruit juice (greater than 1 quart daily)... 

The resistance posed by newly developing strains of bacteria is a major cause of concern for researchers involved in developing antibiotics worldwide. The enzymes responsible for inactivating the /3-lactam antibiotics are known as /3-lactamases. However, many azetidin-2-ones have shown promising inhibitory activity on these /3-lactamases. 2-Oxo-4-phenylazetidin-l-yl naphthalene-2-sulfonate 561 has been shown to inactivate the class A TEM-1 /3-lacta-mase <2000T5719, 1995JA5938>. 

The area covered by natural products chemistry is boundless as it deals with nature itself. There is literally no limit to the topics to be dealt with. This volume 29 continues the tradition of supplying us with superb review articles written by experts. The articles in this volume deal with the screening, isolation, structure, synthesis, biosynthesis, and pharmacology of plant and microbial natural products that exhibit antimitotic, cancer chemotherapeutic, enzyme inhibitory, antiinflammatory, antibiotic and molting hormone activities. The compound types also cover a huge range of natural products, i.e., polyketides, terpenoids, sugars, alkaloids, proteins, and enzymes. 

A simple procedure to prepare 5-aryl- and 5-pyridyl-2-furaldehydes from inexpensive, commercially available 2-furaldehyde diethyl acetal was reported. The reaction proceeded in a four-step, one-pot procedure and the yield of coupling step was usually between 58-91% <02OL375>. A facile route to 3,4-furandicarboxylic acids was developed. DDQ-oxidation of 2,5-dihydrofuran derivatives, which were produced from dimethyl maleic anhydride, furnished the desired esters of furan-3,4-dicarboxylic acid <02S1010>. The furan-fused tetracyclic core of halenaquinol and halenaquinone possessing antibiotic, cardiotonic, and protein tyrosine kinase inhibitory activities was synthesized. Intramolecular cycloaddition of an o-quinodimethane with furan gave the adduct as a single isomer via an enrfo-transition state, which was converted to trisubstituted furan by oxidation-elimination reactions <02T6097>. 

Selvankumar N, Kumar V (1998) Inhibitory activity of trifluoperazine against Mycobacterium tuberculosis in Non Antibiotics - A New Class of Unrecognized Antimi-crobics. NISCOM, New Delhi, pp. 176-182... 

Balmoralmycin (232), isolated from Streptomyces sp. strain P6417, displays an inhibitory activity against protein kinase C (IC50 50 M), an important enzyme in context with cellular transduction mechanisms [165]. Structurally, 232 is nearly identical with the antifungal antibiotic C104 (197) [153], which lacks an oxygen... 

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