Topoisomerase Inhibitors Addressing Fluoroquinolone Resistance in Gram-Negative Bacteria.

Since their discovery over 5 decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC quinolone resistance determining region, have eroded the utility and threaten the future use of this vital class of antibiotics. Herein we describe the discovery and optimization of a series of 4-(aminomethyl)quinolin-2(1H)-ones, exemplified by 34, that inhibit bacterial DNA gyrase and topoisomerase IV and display potent activity against ciprofloxacin-resistant Gram-negative pathogens. X-ray crystallography reveals that 34 occupies the classical quinolone binding site in the topoisomerase IV-DNA cleavage complex but does not form significant contacts with residues in the quinolone resistance determining region

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Not AvailableThree non-descript goat populations, viz. Kumaoni and Garhwali of Uttarakhand hills, and Rohilkhandi of upper Ganges alluvial plain of Uttar Pradesh (India) were characterized phenotypically with standard morphometric parameters. The animals were also evaluated for their reproductive and production performance. The null hypothesis that Garhwali, Kumaoni and Rohilkhandi goat populations are same was tested using value of discriminant functions (D), Wilks’ Lambda and Box’s M statistics. The classification results revealed that 84.9% of all the goats were correctly classified to their own population. This could be used by livestock development agencies to take up appropriate breeding program for the improvement of native stock for future genetic conservation. The milk composition of Uttarakhand goats did not differ much due to geographic identities except for milk fat percentage. The study revealed that body height, body length, horn pattern, face length, and chest girth were the most discriminating and unique variables to separate Rohilkhandi, Kumaoni and Garhwali goat populationsNot Availabl