Abstract
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 TNF-$\alpha $, IL-1$\beta $, 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.
Highlights
One of the essential types of cells in the human immune system is macrophages
Under all conditions, including the negative control, which was treated with dimethyl sulfoxide (DMSO), the positive control, which was treated with combination of LPS and DMSO, and 50 μ g/mL, 75 μ g/mL, and 100 μ g/mL of RHE 231 or RHE 238 with or without LPS, macrophages had 100% cell viability (Figure 1)
Cytokine production becomes a primary concern as in chronic situations stimulated or activated macrophages produce excessive amounts of proinflammatory cytokines and prolonged exposure of the tissue resident cells may eventually lead to tissue injury [15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]
Summary
One of the essential types of cells in the human immune system is macrophages They play a significant role in the development of a proper immune response. Other than their direct effect via cytokine production and phagocytosis they activate other immune cells by antigen presentation [1,2,3,4,5,6,7]. Stimulated or activated macrophages produce proinflammatory cytokines in response to danger signals and these signals lead to inflammation in the tissue [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. After elimination of the danger, antiinflammatory cytokines are produced and macrophages produce some of these to clear the tissue and start the wound healing process [1,2,3,4,5,6,7,8,9,10,11,12,13,14]
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