Synthesis, DNA-binding ability and anticancer activity of benzothiazole/benzoxazole–pyrrolo[2,1-c][1,4]benzodiazepine conjugates

Synthesis and antitumor activity evaluation of new 2-(4-aminophenyl)benzothiazole derivatives bearing different heterocyclic rings

“…Furthermore, compounds 9-15 vary from compounds 3-9 due to including chlorine atom on phenyl ring at second position of the benzothiazole structure. Imidazole including compounds namely N-[4-(benzothiazole-2-yl)phenyl]-2-[(1,5-diphenyl-1H-imidazole-2-yl)thio]acetamide derivatives (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) have methyl, methoxy and fluoro substituents on phenyl groups at the first and fifth positions of the imidazole ring. Among the nine tested compounds, imidazole and non-substituted benzimidazole including compounds (3, 10 and 16) possessed higher activity.…”

“…Phortress (NSC 710305, dihydrochloride salt of the lysylamide prodrug of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203)), the fluorinated water-soluble pro-drug, which has been synthesized to address formulation and bioavailability issues related to the desired parenteral administration [15][16][17][18][19] , was then chosen for phase 1 The mechanism of action involves formation of reactive intermediates that can bind covalently to DNA and can be metabolized only by sensitive cancer cell lines 21 . Conversely, in insensitive cell lines, neither retaining nor metabolization occurs, thereby selective antitumor properties appear due through to metabolism [22][23][24][25][26] . Motivated by the above observations and extending our previous study 27 , we planned to synthesize new 2-(4-aminophenyl)benzothiazole derivatives including (benz)imidazole/benzoxazole/benzothiazole heterocyclic ring systems and to evaluate their antitumor activity against nine cancer types comprised of approximately 60 cell lines.…”

Pyrrolobenzodiazepines as Sequence Selective DNA Binding Agents

“…[61][62][63][64][65][66][67][68][69][70][71][72][73] A series of PBD conjugates by linking different DNA interacting ligands such as benzimidazoles, benzothiazoles, naphthalimides, aryl substituted naphalens, chalcones and poly-aromatic hydrocarbons (pyrene amine, chrysene amine and phenanthrinephenyl) by using varying linker length to enhance the DNA binding affinity and antitumour activity. PBDmorpholine, N-methyl piperizine and N,N-dimethyl amine hybrids have been prepared in an attempt to improve the water solubility and cytotoxicity of the PBD compounds.…”

“…With regard to the PBD scaffold it is well established that it forms a covalent linkage at the N2 position of a guanine base of the DNA while the other subunit of this new conjugate is likely to interact within the DNA through the non-covalent interactions. [63,76] This aspect has been investigated in detail in case PBD-naphthalimide and benzimidazole conjugates examine their sequence selective binding ability.…”

New spiroindolinones bearing 5-chlorobenzothiazole moiety

“…Sunitinib malate (SU11248) (X), the first oral drug acting as a multitarget tyrosine kinases inhibitor, has been approved for the treatment of gastrointestinal stromal tumors, renal cell carcinoma and several authors recall how the combination of SU11248 represent a promising novel treatment strategy against tumors (Figure 1) 17 . Benzothiazole derivatives are highly selective and potent antitumor agents [18][19][20][21][22] . Analysis of their structure-activity relationships shows that most of these compounds possess a second aromatic ring linked directly to the 2-position of benzothiazole ring or through an amine, an amide or an urea moiety.…”