Sequential Cytotoxicity: A Theory Examined Using 2, 6 diphenyl Piperidine-4-one scaffold

The concept of sequential cytotoxicity indicates the successive release of two or more cytotoxic
compounds causing grater toxicity to the neoplasm than normal cell. This hypothesis is evaluated by
designing a series of compounds of 2, 6 diphenyl piperidine-4-one. Recently for the development of
novel cytotoxic and anticancer agents, different series of compounds have been designed that utilizes
the 1, 5-diaryl-3-oxo-1, 4-pentadinyel pharmacophore. These compounds interact with cellular thiols
of cell and thiols are not part of nucleic acids. Hence these compounds are free from the problem of
mutagenicity and carcinogenicity. The series of compounds which either lacking of olefinic bond or
one or more olefinic bond are synthesized by Claisen-Schmith reaction. The compounds having one
or no any olefinic bonds will be predicted to be less cytotoxic than the compounds having two or three
olefinic bonds. The SRB-assay method was used to evaluate cytotoxic property of all the synthesized
compounds. The results revealed that the predictions made regarding the viability of the theory of
sequential cytotoxicity were fulfilled.