Abstract
In our continued attempts at designing new antibiotics based on the structure of the C-9154 antibiotic, to simultaneously improve activity and lower toxicity, an analogue to the C-9154 antibiotic and six derivatives of this analogue were synthesized. The approach was to significantly reduce the polarity of the synthesized analogue in the derivatives to achieve increased permeability across cell membranes by conversion of the highly polar carboxylic group to an ester functional group. The compounds were synthesized using a two-step reaction which involved an additional reaction between benzyl amine and maleic anhydride and then conversion of the terminal carboxylic acid functional group to an ester functional group using a thionyl chloride mediated esterification reaction. The compounds were fully characterized using Infrared, GC-MS, and 1D and 2D NMR experiments. The in vitro biological activity of the compounds showed that the derivatives were more active than the analogues as was anticipated with minimum inhibitory concentration in the range 0.625–5 μg/mL. The analogue had minimum inhibitory concentration in the range 2.5–10 μg/mL. These values are significantly better than that obtained for the original C-9154 antibiotic which had activity in the range 10–>100 μg/mL.
Highlights
In 1889, Vuillemin, a French bacteriologist, suggested using the word “antiobiosis”, meaning “against life,” to describe the group of drugs that had action against microorganisms [1]
In our continued attempts at designing new antibiotics based on the structure of the C-9154 antibiotic, to simultaneously improve activity and lower toxicity, an analogue to the C-9154 antibiotic and six derivatives of this analogue were synthesized
The term “antibiotic” as coined by Selman Waksman is used to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution
Summary
In 1889, Vuillemin, a French bacteriologist, suggested using the word “antiobiosis”, meaning “against life,” to describe the group of drugs that had action against microorganisms [1]. Antibiotics today, with advances in medicinal chemistry, are semisynthetic modifications of various natural compounds [4]. Some antibiotic compounds are still isolated from living organisms like the aminoglycosides, whereas other antibiotics like the sulfonamides, the quinolones, and the oxazolidinones are produced solely by chemical synthesis [4]. During studies on screening for antibiotics that showed activity against bacteria resistant to various known antibiotics, a new antibiotic with a broad antibacterial spectrum was isolated from the whole agar culture of Streptomyces strain NR-7GGI. This Streptomyces species was called Streptomyces kurssanovii and the isolated antibiotic referred to as fumaramidmycin [5]. These analogues were shown to have antibacterial activity against Staphylococcus aureus and Escherichia coli ranging from 15 μg/mL [10] to 4000 μg/mL [9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
