Eureka! Institutional Repository

Objectives Due to the constantly increased necessity of discovering innovative substances which can carry antibiotic effects, the current research thesis project has as an aim - by means of computational screening - to examine a number of newly synthesized chemical compounds for their potential inhibitory effect against E. Coli’s gyrase, by having as a purpose the development of new antibiotics and the investigation of novel compounds which had their antimicrobial activity confirmed. Materials and Methods For the completion of this study a number of 78 chemical compounds was used ( group A of compounds ), which exhibit a vast structural diversity. They differentiate, due to their structure, into 8 subgroups and those are I. Thiazole, II. Thiomorpholines, III. Derivatives of Pyrimidines, IV. Derivatives of Cinnamyl Alcohol, V. Derivatives of valproic acid, VI. Derivatives of tyrosine, VII. Derivatives of gallic acid, and VIII. Derivatives of serine. Apart from the aforementioned compounds, N-(2-phenyl-4-oxo-1,3-thiazolidin-3-yl)-1,2-benzothiazole3-carboxamides and acetamides were used ( group B of compounds ), which have already their antimicrobial effect confirmed. The computational prediction of their effect by using the Docking method was based on the formation of the most energy stable structure of those compounds. The study for predicting their effect has been performed through the use of the open source software PyRx, which actualizes molecular docking analysis of micromolecular compounds that is supported by Autodock Vina. The identification of E. Coli gyrase’s amino acids that interact with the aforementioned compounds has been done with LigPlot+. Results From the 78 compounds that have been checked, 22 of them had presented a strong docking and inhibitory probability for the DNA gyrase, with those that have been selected to show interaction with the amino acids that were posed as reference point – derived from a known inhibitor – but also having their free binding energy values less than -5 kcal/mol ( compounds of group A ). The analysis for the rest 21 compounds, which pertain to group B (3h, 3i, 3j, 3o, 3p και 4a-4p), has shown that all of them could be gyrase inhibitors as they have exhibited binding energy <-6.5 kcal/mol. The compounds that have been tested (3h, 3i, 3j, 3o, 3p και 4a-4p), have presented inhibitory activity to all the bacterial species which have been examined to, likewise to E. Coli, but with diverse levels to each one. Conclusion This study is part of a more thorough research study and for its completion demands the in vitro examination of gyrase’s inhibition which will allow us to evaluate the effectiveness of the docking method and to readjust its respective parameters where its further optimization is the final goal. Thus, from the 78 compounds of group A, 22 of them seem to have a positive inhibitory potential of E. Coli’s gyrase and their effect should be investigated - in a later time - in vitro, whereas all the compounds of group B have, also, demonstrated positive inhibitory potential of gyrase, in relation to the one that known inhibitors of the enzyme have shown