In vitroantitumour activity, safety testing and subcellular distribution of two poly[oxyethylene(aminophosphonate-co-H-phosphonate)]s in Ehrlich ascites carcinoma and BALB/c 3T3 cell culture systems

Abstract

Two polyphosphoesters containing anthracene-derived aminophosphonate and hydrophilic Hphosphonate repeating units, poly[oxyethylene(aminophosphonate-co-H-phosphonate)]s (1 and 2), were tested for the in vitro antitumour activity on cell cultures derived from ascitic form of Ehrlich mammary adenocarcinoma by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-dye reduction assay. The in vitro safety testing of the copolymers was performed by BALB/c 3T3 neutral red uptake assay. A study on their uptake and subcellular distribution in nontumourigenic and tumour cells was performed by means of fluorescence microscopy. Both copolymers showed significant antitumour activity towards Ehrlich ascites carcinoma (EAC) cells. However, the in vitro safety testing revealed significant toxicity of polymer 2 to BALB/c 3T3 mouse embryo cells. In contrast, polymer 1 showed complete absence of cytotoxicity to BALB/c 3T3 cells. The fluorescent studies showed that the substances were diffusely distributed in the cytoplasm in both cell culture systems. As opposed to BALB/c 3T3 cells, in EAC cells, intense fluorescent signal was observed in the nuclei and in the perinuclear region. The tested polyphosphoesters are expected to act under physiological conditions as prodrugs of aminophosphonates.

Synthesis and Anti-Pancreatic Cancer Activity Studies of Novel 3-Amino-2-hydroxybenzofused 2-Phospha-γ-lactones

“…The recent reports on the biological activity evaluation studies of organophosphorus heterocycles reveal that this is a search thrust area with perpetual contributions . Such inherent anticancer potentiality of α-aminophosphonates − has inspired us to design and synthesize some new 3-amino functionalized benzofused phospha-γ-lactones with a potential core of the 2,5-dihydro-1,2-oxaphosphole-2-oxide moiety and investigate their pancreatic cell inhibition activity. Meanwhile, the previous methodologies for the synthesis of benzofused 2-phospha-γ-lactones involves the utility of precursors like aldols, divinyl ethers, acetylene carboxylic acids, chalcones, allenes, , and alkynyl systems − along with phosphorylating agents like dichlorophenylphosphines, ,, dichlorophenyl phosphineoxides, triphenyl phosphine, , trialkylphosphite, 3-methylbuta-1,2-dien-1-ylphosphonic dichlorides, allenyl phosphonates, and dialkyl phosphites. , The present route for the synthesis of 2,5-dihydro-1,2-oxaphosphole-2-oxide core is highly adaptable with simple reaction procedures and hence eliminates the use of expensive precursors (Figure ).…”