Abstract:
Over a long exposure of drugs through chemotherapy cancer cells develops
drug resistance due to which drug is no more effective on cancer cells. To
overcome this problem scientists are trying to target a specific organelle in cells
such as nucleus, endoplasmic reticulum (ER), mitochondria etc. In this context,
we have hypothesised an approach to target a specific organelle of cancer cells,
to inhibit a particular enzyme that reduces the chance of cancer cells
proliferation. We are mainly interested here to target mitochondria, as
mitochondria are being found to be a key factors in biomedical science, and so
inhibit the inducible COX-2 enzyme by using selective COX-2 inhibitors like
Indomethacin and Ibuprofen, present inside the mitochondria as reported in
many literatures. To target mitochondria specifically we have synthesised small
molecules attached with a positively charged moiety that helps the molecules to
drag and internalise towards mitochondrial negatively charged membrane. For
the positive charge different derivatives of Triphenylphosphine (TPP) have been
used, simultaneously it is also demonstrated that which of the derivatives is
more effective in cellular internalizing the small molecules inside
mitochondria, cell viability has been reported by MTT assay using MCF-7 cells
which has reported good amount of killing in comparison to free drug. In order
to further check the cellular internalization fluorescence compound has been
synthesized of the same COX-2 inhibitors. The results suggest that these small
molecules can be used to inhibit COX-2 by specifically targeting the
mitochondria. Hence, by doing so we can demonstrate which among a particular
inhibitor attached to one of the TPP derivatives is more efficient as cancer
treatment approach.
