Background::
Inflammatory diseases are one of the major concerns of today’s world, major disorders caused by
inflammation includes, allergy, asthma, arthritis, hepatitis, autoimmune diseases, celiac disease etc. During most of these
events, many protein and molecules expression were modulated and one such protein is AP-1 (c-Fos-c-Jun heterodimer
complex). AP-1 is a dimeric protein activated by several physiological stimuli and environmental insults such as growth factors,
polypeptide hormones, neurotransmitters, cytokines, cell-matrix interactions, UV irradiations, viral and bacterial infections.
Objective::
Present study is mainly focus on designing of small molecule analogs to inhibit c-Fos-c-Jun complex, as the
complex is involved in many inflammatory diseases and precisely involved in disease progression. Therefore, it had been
considered as therapeutic target since more than a decade.
Methods::
In the present study, an attempt was made to design the analogs of referral drug T-5224. 31 analogs of T-5224
were designed by chemoinformatics approach and subjected to ADMETox for screening.
Results and Discussion::
Among the 16 compounds were found to pass the evaluation, all 16 compounds passed the toxicity
evaluation except 7th molecule. The molecular docking study showed that the compounds 1, 2 and 16 were having high inhibition
constant.
Conclusion::
The preliminary results suggest the compounds 1, 2 and 16 are having the potential ligand binding capacity
with cFos-cJun complex. Further analysis, with advanced tools, may results in potential small molecule to inhibit the c-Fosc-
Jun complex.
Better living through chemistry: Addressing emerging antibiotic resistance