Development of novel anti-mycobacterial agents is an urgent challenge to eradicate the increasing emergence and rapid spread of multidrug-resistant strains (MDR). Filamentous temperature-sensitive protein Z (FtsZ), a highly conserved protein in prokaryotes, is a crucial cell division protein. As inactivation or alteration of FtsZ assembly results in cell division inhibition and consequently cell death, FtsZ is considered a promising antibacterial target. With the aim to find potent and novel anti-mycobacterial agents, a series of N 1 -(benzo[d]oxazol-2-yl)-N 4 -arylidine compounds (6a-o) were designed and synthesized following a molecular hybridization approach. Activity of the synthesized compounds was evaluated against drug-sensitive, multidrug-resistant and extensive-drug resistant Mycobacterium tuberculosis (Mtb). Compounds 6b, 6c, 6l, 6m and 6o showed promising anti-mycobacterial activity with MIC range of 0.48 – 1.95 µg/mL, with low cytotoxicity againt human non-tumorigenic lung fibroblast WI-38 cells. In addition, activity of the compounds 6b, 6c, 6l, 6m and 6o was evaluated against bronchitis causing-bacteria. Interestingly, they exhibited good activity against bacteria causing bronchitis; S. pneumoniae, K. pneumoniae, M. pneumoniae and B. pertussis with MIC range of 0.24 – 7.81 µg/mL. Furthermore, compounds 6b, 6c, 6e, 6f, 6j, 6l-6o were evaluated as E. coli Ftsz GTPase inhibitors. Molecular dynamics simulations of Mtb FtsZ protein-ligand complexes identified the interdomain site as the binding site and key interactions. Additionally, density function theory (DFT) studies of the compounds 6c, 6l and 6n were performed to investigate E/Z isomerization. Compounds 6c and 6l are present as E-isomers and compound 6n as an in E/Z mixture. Our preliminary results provide the lead for the design of more potent and selective hybrid anti-mycobacterial drugs. M. tuberculosis stimulates the macrophage to rapidly secrete vascular endothelial growth factor (VEGF) extracellularly so there is a relationship between tuberculosis and VEGF over secretion so this is my starting point in designing and synthesis of novel agents inhibit both tuberculosis and VEGFR-2 which have dual –antitubercular/anti cancer- activity. Accordingly, two series of new compounds N`-(benzo[d]oxa/thiazol-2-yl)-2-(5-aryl-4-phenyl-4H-1,2,4-triazol-3-ylthio) acetohydrazide (11a-j), N`-(benzo[d]oxazol-2-yl)-2-(5-aryl-4-phenyl-4H-1,2,4- triazol-3-ylthio) propanehydrazide (11k,l) and N-(4-un/substituted phenyl)-Nun/substituted-2-((3-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6- yl)thio)acetamide (16a-e) were designed and synthesized following a molecular hybridization approach. Activity of the synthesized compounds was evaluated against drug-sensitive, multidrug-resistant and extensive-drug resistant (Mtb). Compounds 11h, 11i, 11l and 16c that showed the highest activities against all Mtb strains were selected for enoyl-acyl carrier protein reductase inhibition assay. The most active anti-mycobacterial compound 11h was observed to be the most potent InhA inhibitor (IC50 = 1.3 μM), IC50 range of compounds 11h, 11i, 11l and 16c against InhA = 1.3 - 4.7 μM. The synthesized compounds (11a-l and 16a-e) were in vitro evaluated against VEGFR-2 activity. The obtained results revealed that the synthesized compounds showed promising activity on VEGFR-2. Besides, the compounds were in vitro assessed against topoisomerase II. However, they showed weak activity on topoisomerase II. Based on the results obtained from VEGFR-2 inhibition, the most active compounds (11a, 11c, 11e, 11f, 11h, 11l, 16a, 16d and 16e) were selected for further evaluation of the anti-proliferative activity against two cancer cell lines, (A549) and (HepG2) using MTT assay protocol. Generally, compounds 16d and 11e were found to be the most anti-proliferative compounds against the two tested cancer cell lines. The safety profile of the most active compounds were of low cytotoxicity against normal adult liver epithelial cells (Transformed Human Liver Epithelial-2, THLE-2 cells). Compounds 11e and 16a have apoptosis percentages of 40.20% and 32.20%, respectively, which are more than the control (0.51%). Furthermore, compound 11e and 16a significantly increased the level of caspase-3 (4.1-fold and 3.6-fold, respectively) when compared to control cells.