Basic Informations

C.V

Master Title

Synthesis and Antimicrobial Activity of Some New Heterocyclic Derivatives

Master Abstract

Several new benzothiazole hybrids with other heterocyclic structures were synthesized in an attempt for exploring a new class of antibacterial, antifungal and antibiofilm agents. These derivatives include 2-(5-cyano-1,6-dihydro-6-oxo-4-arylpyrimidin-2-ylthio)-N-(6-substituted benzo [d] thiazol-2-yl)acetamide IVa-n, 2-imino-3-(6-substitutedbenzo[d]thiazol-2-yl)-5-(4-(un) substituted arylidenyl)thiazolidin-4-one VIa-l and 3-(6-Substitutedbenzo[d]thiazol-2-yl)-2-((N,N-disubstituted amino methyl)imino) thiazolidin-4-one VIIa-f. The target compounds were synthesized starting from 6-substitutedbenzo[d]thiazol-2-amine Ia, Ib and their structures were elucidated on the basis of elemental analyses and spectral data. These compounds were screened for their antibacterial activity against gram-positive bacteria (B. subtilis, S. lutea and S. aureus), gram-negative bacteria (E. coli ATCC 25922, E. coli ATCC 5087, P. aeruginosa and P. vulgaris) and antifungal activity against C. albicans through the sensitivity test using cup plate method. Minimum inhibitory concentration was measured for the only active compounds using agar dilution method. It was shown that the two classes incorporating the 2-imino-thiazolidin-4-one structure showed more antibacterial and antifungal activities and more pronounced MIC values than the class incorporating the dihydropyrimidinone. Additionally, the antibiofilm activity of the most active compounds VIa, VIb, VIg, VIh, VIj, VIk, VIIc, VIId, VIIe and VIIf as antifungals comparing to fluconazole were screened against 2 pathogenic Candida isolates CA1 and CA2 using the fluconazole as the model system. Biofilm growth was monitored semiquantitatively by colorimetric assay using the crystal violet as indicator.

PHD Title

“Design, synthesis and antitumor evaluation of new benzothiazole derivatives”

PHD Abstract

The present thesis pointed for the benzothiazole molecule as a future therapeutic lead of developing new anticancer agents. In the present work, a new series of benzothiazoles hybridized with pyrimidine moiety was designed and synthesized using the lead compound IVa. Various chemical modifications on the pyrimidine ring of IVa at four different positions were done in a trial to get new multi-targeted anticancer agents. All final synthesized derivatives were submitted to the National Cancer Institute (NCI), USA, to be screened for their in vitro anticancer activity. Further evaluation for the cytotoxic activity of the most active compounds was performed using the MTT assay method. Compounds IVd, VIIId, VIIIh, VIIIi and XVII, displayed the highest anti-proliferative activity, compared to erlotinib against specific cell lines. Compounds IVd, VIIId, VIIIh, VIIIi and XVII were then selected for examining their in vitro enzyme inhibitory activities against the EGFR, HER2 and TS enzymes using lapatinib and 5FU as standards. Furthermore, cell cycle analysis and apoptosis induction detection were also evaluated. Finally, molecular docking studies were carried out for all final synthesized compounds to interpret their observed enzymatic activities based on the ligand-protein interactions.