Background: Bacterial resistance to antibiotics is an overwhelming serious problem worldwide. This necessitates searching for novel sources of antibiotics. Chloramphenicol resistance is mediated through the plasmid-encoded acetyltransferase gene. Objectives: Design of novel antimicrobial chloramphenicol analogs and screening of their in vitro antibacterial activity in Egypt to overcome the bacterial resistance against chloramphenicol. Methods: Our study type was a screening experimental study. In our study, in vitro antimicrobial novel chloramphenicol analogs activity semi-synthetically produced from Streptomyces species in Egypt was evaluated by standard agar dilution technique determining their minimum inhibitory concentrations (MICs) of growth of different pathogenic bacteria in Egypt. Chloramphenicol was purified by column chromatography, then modified by chemo-informatics. Replacement of the phenyl group of chloramphenicol with the nitrothienyl group produced chloramphenicol analog A(chlornitrothienylcol). Also, the replacement of the p-nitro group with the acetyl group constituted chloramphenicol analog B (acetophenicol). Results: Both analogs were more active antibacterial agents than chloramphenicol but had less bacterial resistance than it. Both analogs had MICs of less than 10 micrograms/ml for bacterial growth.