Cervical cancer is the second largest form of cancer to infest the leading cause of death in women worldwide.
There are many causes of cancer but viruses are the most common among them. Human papillomaviruses (HPVs) are
found to be the causative organism in almost 99.7% of the cases. HPV16 is the most frequent HPV type in malignant
neoplastic growth in about 60% of cervical carcinoma cases. There is limited success achieved in surgical removal or by
immune modulation and more effective therapies are under investigation. Observing the mortality rate we theorize a need
for alternative treatment approaches and propose a blueprint of compounds with desirable properties that may lead to the
development of drugs to treat HPV-associated neoplasias.
E6 oncoprotein of HPV16 has a potential zinc finger domain critical for binding to E6AP, causing p53 degradation and
malignancy. Some azoics and disulfides were selected depending on their affinity towards E6 zinc finger and thereby
preventing E6-E6AP complex formation. Combinatorial nontoxic derivatives of these azoics and disulfides were docked
and validated against the oncoprotein to inhibit E6-E6AP interaction.
Among these, two compounds (E)-N-(2-amino-2-oxoethyl)-N-(4-chlorophenyl) diazene-1,2-dicarboxamide and (E)-N-(2-
amino-2-methylpropyl)-N-(thiophen-2-yl)diazene-1,2-dicarboxamide showed binding affinity of -23.70, -19.53 and
-5.49, -4.65 Kcal/mol respectively in FlexX and Autodock4.2. These compounds are found more effective than those of
the approved E6-E6AP binding inhibitors. Pharmacophores of these compounds were generated to confirm it with pharm
The study may confer the way of design of new mechanism and new compounds to treat cervical cancer.