Illnesses caused by microbial species, such as Mycobacterium tuberculosis (M. tb) are one of the leading the causes of mortality worldwide1. The emergence of drug- resistant strains of microbes has led to an urgent demand of novel antibiotics. Derivatives of 1,10-phenanthroline (phen) and their metal complexes have been shown to possess antimicrobial effects2. The first part of research carried out in this study involves synthesis and characterisation of oxazine-based derivative of phen and its Ag(I), Cu(II) and Mn(II) complexes. The antimicrobial effects of this ligand and its metal complexes were studied using a Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and a fungal (Candida albicans) strain. In addition, lipophilic derivatives of the oxazine-based phen derivatives and its Cu(II) complexes were also prepared, characterised and screened against Gram-positive bacterial strain. The toxicity of all of these ligands and their complexes was also studied using the greater wax moth larvae Galleria mellonella. The Cu(II) complexes were the most active towards the Gram-positive bacteria and the increase in lipophilicity, up to a certain point, displayed an increase in antibacterial activity of the ligand and its Cu(II) complex. The Ag(I) complex was the most active towards the fungal strain. The compounds tested did not display promising activity towards the Gram-negative bacterial strain. All compounds tested were well tolerated by Galleria mellonella. Second part of this research focuses on targeting M. tb by derivatising isoniazid (INH) through Schiff base condensation. A phen-based hybrid of INH is prepared and complexed to Ag(I), Cu(II) and Mn(II) metal ions and the ligand and metal complexes were characterised. The antimycobacterial activity of this ligand and its metal complexes was studied against a drug susceptible and three drug resistant strains of M. tb. The broad-range antimicrobial activity of this ligand and its metal complexes was also studied against Gram-positive (Staphylococcus aureus), Gram-negative (Pseudomonas aeruginosa) and fungal (Candida albicans). The toxicity of these compounds toward the mammalian cell line A549 was also examined. All of the compounds generated displayed promising antimycobacterial activity towards all strain of M. tb and presented SI values >10. The Ag(I) complexes displayed excellent broad range antimicrobial activity.