Abstract
Ph.D. (Chemistry)
Riminophenazines are compounds containing a phenazine ring, with an alkylimino substituent on
one of the benzene rings, and can have other substituents anywhere else on the tricyclic core. In
this project, the synthesis of riminophenazines and their test for anti-TB effect, as well as their
redox activities were researched. The compounds were synthesized using known procedures by
manipulating the nature of the groups used in the annulation to assemble these structures. In the
course of the project, glyoxalinophenazines were unexpectedly formed when pure acetic acid
was used in the Clemmensen reduction of the dimethyl- and diethyl-aminoethyl-phenyl-4,6-
dinitrobenzene-1,3-diamine derivatives. To our knowledge, this was never done before.
Reducing the dinitrogroups under catalytic hydrogenation conditions gave the anticipated
riminophenazines.
A series of new riminophenazine derivatives with linear and branched alkyl substituents on the
imino nitrogen were designed and obtained with the aim to reduce their lipophilicity relative to
that of the known anti-leprosy drug clofazimine, and to lower their toxicity whilst upholding
high anti-tubercular activity. Selected compounds thus synthesized had their lipophilicity
calculated and found to be lower than that of clofazimine. They were subsequently screened for
mammalian cytotoxicity, evaluated against Mycobacterium tuberculosis H37Rv strain, and their
redox activity determined. Of the 30 compounds tested against the TB strain, 3 proved to be
active. Furthermore, all the compounds displayed fully reversible redox cycles.
The exploration into the synthesis of the expanded ring system to furnish riminodiazepineanalogues
was, however, unsuccessful.