A series of symmetric bis-benzoxazole derivatives were synthesized using one-pot cyclization between 4-chloro substituted 2-aminophenol and suitable dicarboxylic acids. Synthesized compounds' anticancer activities were tested by using MTT assay on human prostate (DU145) and breast (MCF7) cancer cells. Screening results revealed that all compounds possessed a high level anti-cancer potential by significantly decreasing the cell proliferation in prostate and breast cancer cell lines. Our compounds exerted their anti-proliferative effects in a dose and time dependent manner. Our results suggest that they can be highly potent since they were biologically active even at low concentrations. Our study presents a series of new bis-benzoxazole based compounds with potential therapeutic effects against tumor cells. Therefore, characterization of new generation bisbenzoxazole derivatives will have a significant contribution on the development of new era anticancer drug candidates.

Benzoxazoles and their derivatives have exerted anti-cancer and anti-inflammatory (immunomodulatory) potential due to their anti-proliferative effect on the cells. These molecules are DNA basebioisosteres, therefore, their mechanism of action could be by mimicking the structures of the DNA bases and halting the DNA polymerization processes. Based on their anti-proliferative effect, in our study we aimed to decipher the potential anti-inflammatory activities of unique bisbenzoxazole derivatives in vitro on mammalian macrophages. Being able to manipulate the inflammatory function of macrophages would enable the regulation of the immune response against danger stimuli. This would enable us better prognosis against different types of the diseases ranging from autoimmune disorders to cancer. Our results support the stark anti-inflammatory potential of bisbenzoxazole derivatives RHE 241 and RHE 248 in vitro on the LPS activated mammalian macrophages. After further delineation of their mechanism of action in vitro and their in vivo potency, these molecules could be utilized as potent anti-inflammatory medicines.

Benzoxazoles are DNA base bioisosteres and studies suggest that their derivatives have antiproliferative activities. Based on their antiproliferative activities they have been mostly studied as new generation anticancer drugs. In our study we exploited their antiproliferative effect, aiming to delineate bisbenzoxazole derivatives' (RHE 231 and RHE 238) potential antiinflammatory effect on mouse macrophages that are activated in vitro through danger signal LPS stimulation. RAW 267.4 mammalian macrophages were activated in the presence of our derivatives with or without danger mimic E. coli derived LPS. We present data that support the strong antiinflammatory activity of the bisbenzoxazole derivatives RHE 231 and RHE 238 on stimulated mammalian macrophages. There was a significant and substantial decrease in the production levels of TNFα , IL-1 β , and IL-6 proinflammatory cytokines in the presence of RHE 231 and RHE 238. These molecules had an antiproliferative effect on the macrophages and, probably, this was their mechanism of action on the cells to alter their inflammatory functions. Our results show that bisbenzoxazole structures RHE 231 and RHE 238 have potential to be used as antiinflammatory drug agents.

A series of symmetric bis-benzoxazole derivatives were synthesized using one-pot cyclisation reaction between 4-fluoro substituted 2-aminophenol and suitable carboxylic acids. Synthesized compounds' anticancer activities were tested by using MTT assay on human prostate (DU145) and breast (MCF7) cancer cells. Screening results revealed that all compounds possessed a high level anti-cancer potential by significantly decreasing the cell proliferation in prostate and breast cancer cell lines. Our compounds exerted their anti-proliferative effects in a dose and time dependent manner. Our results suggest that they can be highly potent since they were biologically active even at low concentration ranges. Our study presents a series of new bis-benzoxazole based compounds with potential therapeutic effects against tumor cells. Therefore, characterization of new generation bis-benzoxazole derivatives will have a significant contribution on the development of new era anti-cancer drug candidates.