Other modifications of established antibiotics classes

Numerous additional reports of new antibiotic analogs have been published recently with notable examples cited here. While not strictly speaking 'antibacterial agents' p-lactamase inhibitors have found utility, particularly when paired with a specific antibiotic (e.g., Augmentin) [61]. The penem sulfone SA-2-13 11 was designed as a class A p-lactamase inhibitor using the crystal structure of tazobactam bound to the p-lactamase E166A SHV-1 as a guide. In tests, the trans-enamine intermediate formed by the SA-2-13 with sHV-1 was found to be 10 times more stable than the analogous tazobactam intermediate [62]. A new 6-alkylidenepenicillanic acid sulfone LN-1-255 12, a potent inhibitor of serine p-lactamases, was shown to dramatically lower the MICs of cefpirome and ceftazidime against highly resistant Enterobacteriaceae [63]. A novel non-p-lactam inhibitor NXL104 13 has been shown to irreversibly inhibit both class A and class C p-lactamases [64,65]. In experiments with highly resistant Enter-obacteriaceae, NXL104 restored rapid bactericidal activity to ceftazidime. NXL104 entered Phase I clinical trials in 2007.

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BAL19403 14 is a new macrolide that is highly potent against erythromycin-resistant and clindamycin-resistant propionibacteria [66,67]. Potent antiinflammatory activity and good pre-clinical safety make BAL19403 a good candidate for topical treatment of acne [68-70]. AR-709 15 is a new di-aminopyridine in Phase I clinical trials derived from a program aimed at optimizing dihydrofolate reductase (DHFR) inhibitors treating respiratory infections caused by multi-drug-resistant Streptococci, Pneumococci, and Staphylococci [71-73]. In enzyme assays using wild-type and mutant DHFR isolated from S. pneumoniae and S. aureus, the IC50 for AR-709 was 12 x-60 x lower than for trimethoprim (TMP) for the wild-type and 50-100 x lower for the mutant enzyme [74]. Accordingly, AR-709 has demonstrably more potent antibacterial activities than TMP against both TMP-S and TMP-R strains of S. pneumoniae and S. aureus. AR-709 is currently in a radiolabelled Human Microdose study where preliminary results indicate that the drug distributes well in the target lung tissue.

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Fight Acne

Fight Acne

I am sure that every one of you is familiar with acne. Almost all of us got this skin disorder, right? Well, technically known as acne vulgaris, this skin disorder affects millions of people from different walks of life, annually.

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