Benzimidazoles are considered one of the most promising bicyclic hetero aromatic nucleus in the field of medicinal chemistry, so we direct our interest for synthesis of novel derivatives and we subject these derivatives for testing the biological activities as anticancer , antimicrobial and anti fungual activities. Benzimidazole derivatives have a wide variety of biological activities as anticancer , antimicrobial, anti ulcer,anti hypertensive , analgesic and anti-inflammatory activity. 1, 3, 4-oxadiazole derivatives have a lot of pharmacological activity, (Furamizole) has anti bacterial activity and (Tiodazosin) has anti hypertensive action. 1,2,4 triazole derivatives possessing many important biological activities as Itraconazole which has broad-spectrum antifungal activity and letrozole used in treatment of postmenopausal women with advanced breast carcinoma. Condensation of acid hydrazideIII with p- toluene sulfonyl chloride &benzoyl acetone afforded sulfonamide derivative IV and pyrazole derivativeV respectively. The key intermediates for this investigation are 1-(2-(1H-benzo[d]imidazol-1-yl)acetyl)-4 –aryl thiosemicarbazideVIa-c which are synthesized by a reaction of acid hydrazide III with isothiocyanate derivatives(SchemeI). . Cyclization of these compounds are performed with different reagents as conc H2SO4& I2/KI to give1,3,4-thiadiazol derivatives VIIa-c and 1,3,4-oxadiazol derivatives VIIIa-c respectively . However thiazole derivatives XIa,b are synthesized by the reaction with phenacyl bromide derivatives as a reagent. Moreover the synthesis of 1,2,4-triazole-3-thiol derivatives IXa-c and 4-amino-3-substituted amino-4-H-1,2,4-triazole derivatives Xa,b via reaction of thiosemicarbazide VIa-c with NaOH&NH2-NH2/ CH3OH respectively (SchemeII). In addition ,alkylation reactions are performed for1,2,4-triazole-3-thiol by chloro acetamide derivatives , ethyl iodide and methyl iodide using NaOH in aqueous ethanol (SchemeIII) . 4- Amino-5-((1H-benzo[d]imidazol-1-yl)methyl)-4H-1,2,4 triazole -3 thiol XIV is synthesized by reaction of thiocarbohydrazide with ester of benzimidazole II. Condensation of this compound with benzaldehyde derivatives is performed in ethanol using glacial acetic acid to produce imine derivativesXIII& XVa-h (SchemeIV&V) . The cytotoxic activity evaluation was performed against two carcinoma cell lines, namely MCF-7(breast carcinoma) and HCT-116(colon carcinoma) using doxorubicin as standard , most of the tested compounds show moderate to weak anti tumor activity while others are inactive . Screening of anti microbial activity is also performed for most of new compounds using cefotaxime and nystatin as standard . Some compounds show high inhibitory activity against gram-positive , gram – negative and fungi, others show moderate to weak activity . Molecular docking into the ATP binding site of EGFR and CDk2 receptor helps in understanding the antitumor selectivity over breast cancer MCF-7 and colon cancer HCT116 cell lines. Molecular docking studies further supported the highest potency of compound XVd and XIII against breast and colon cancer respectively. The crystal structure of epidermal growth factor receptor with erlotinib (TarcevaTM) (PDB code: 1M17) and the crystal structure of CDK2 in complex with ATP (PDB code:1HCK) were retrieved from protein data bank (PDB). Ligands were docked into receptor active site of both epidermal growth factor receptor (EGFR)and cyclindependent kinase 2(CDK2) along with EGFR inhibitor and ATP respectively. Docking of the ligands was performed using Gold suite v5.2.0 (2010).