Syntheses and Biological Activity of Some Derivatives of C-9154 Antibiotic

This research was undertaken to design several new antibiotics, by structurally modifying the C-9154 antibiotic, simultaneously improving its activity and lowering toxicity. This was achieved by synthesizing an analogue to the C-9154 antibiotic and seven derivatives of this analogue. 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 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 analogue as was anticipated and both were more active than the standard drugs used for comparison. Work is ongoing to establish applications for the compounds as antiplasmodials, antivirals, anticancers/tumours, antitrypanosomiasis, anthelminthic, and as general antibiotics for human, veterinary, and even agricultural use as they had marked effect on both Gram-positive and Gram-negative bacteria and some fungi. 1. Introduction Vuillemin (1889), a French bacteriologist, was first to suggest using the word “antibiosis,” (against life) to describe the group of compounds that exhibited biological action against microorganisms [1]. Selman Waksman, the discoverer of streptomycin, later changed this term to antibiotic in 1942 [2]. The term “antibiotic” according to Waksman is used to describe any substance produced by a microorganism that is detrimental to the growth of other microorganisms in high dilution or at low concentration [3]. With current advances in medicinal chemistry, antibiotics are mostly semisynthetic modifications of various natural compounds [4]. These include, for example, the beta-lactam antibiotics, like the penicillins, the cephalosporins, and the carbapenems. Some antibiotic compounds are still being isolated from natural sources, for example, the aminoglycosides, whereas other antibiotics like the sulfonamides, the quinolones, and the oxazolidinones are produced entirely by chemical synthesis [4]. This implies that synthesis of antibiotic compounds plays an important and vital role in the fight against disease-causing organisms. The problem of resistance to antibiotics on the part of the microorganism, the adverse side effects associated with antibiotics in current use, and the difficulty in obtaining these antibiotics in large (commercial) quantities from their natural sources imply that newer antibiotics have to be constantly