Synthesis, characterization and biological studies of chromene derivatives

In this thesis, a series of novel chromene derivatives based on three different moieties of biologically active compounds were synthesized and their antimicrobial and cytotoxic activities were evaluated in vitro. The fluorescent 8-amino-10-phenyl-5-hydroxy-2-oxo-4-propyl-2H, 10H-pyrano [2,3-f] chromene-9-carbonitrile derivatives 2.2(a-j) were synthesized in good yields and with good fluorescence quantum yields (ΦF). The structures were confirmed on the basis of their spectral data and elemental analysis. The antimicrobial activity was investigated and tested against several human pathogens: Gram-positive, Gram-negative bacteria and fungi as well as mycobacterium using agar well diffusion method. Minimum inhibitory concentrations were reported against each pathogen. All compounds showed significantly potent antimicrobial activities against most bacterial strains compared to reference drugs. Due to their structural similarity to reference drugs clorobiocin and novobiocin, docking experiments in the ATP binding pocket of DNA gyrase B enzyme revealed that the compounds mostly have the same binding mode as the reference drugs. Moreover, the cytotoxic activity was also evaluated against four different human cell lines and exhibited more potency than the reference drug. Several new 8-amino-10-phenyl-5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-3,4-diydro-2H,10H-pyrano[2,3-f] chro-mene derivatives 3.2(a-g) were synthesized in good yield. The structures of these derivatives were established on the basis of IR, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC and elemental analysis. All new synthesized compounds were evaluated for in vitro antimicrobial and cytotoxicity activities. Their antimicrobial activity was investigated and tested with seven human pathogenic Gram-positive and Gram-negative bacteria, four fungi and one mycobacterium, using agar well diffusion method, and minimum inhibitory concentrations were reported. Most of the new tested compounds exhibited significant potent antimicrobial activities against most bacterial strains compared to reference drugs. Some of these new synthesized derivatives exhibited the highest inhibitory activity against Pseudomonas aeruginosa (RCMB 010043), Escherichia coli (RCMB 010052) compared to reference drugs. On the other hand, three of these new compounds were found to be more effective against Salmonella typhimurium. The antibacterial activity of most compounds was found to be comparably active to reference drugs against Gram-positive bacteria, while compound 3.2c did not show any antimicrobial activity. The cytotoxic activity was also evaluated against four different human carcinoma cell lines and exhibited good cell growth inhibitory activity against HCT-116 cell line. The molecular modeling results showed binding interaction of some new synthesized compounds in the active site of Gyrase B. A variety of novel derivatives of 2-amino-6-(4-ethoxyphenylazo)-4(-phenyl)-4H-benzo[h]chromene-3-carbonitrile 4.2(a-j) have been prepared via three component reactions. The structures were confirmed on the basis of their spectral data and elemental analysis. Their antimicrobial activity was investigated and tested against four human pathogen Gram-positive and Gram-negative bacteria and four fungi. Some newly prepared compounds exhibited antimicrobial activities against Gram-negative bacteria and fungi species compared to reference drugs. The bathochromic shift of compound 4.2a was shown in solution when acidified. Moreover, the cytotoxic activity was also evaluated against three different human cell lines. Some tested compounds have good IC50 against HCT-116 and MCF-7 cell lines. The molecular modeling results showed binding interaction of some new synthesized compounds in the active site of Gyrase B