Synthesis, in vitro evaluation and computational modelling of benzene sulfonamide derivatives as Dickkopf 1 inhibitors for anticancer drug development.

In the modern age of drug discovery sulfanilamide derivatives are known to have great anti-cancerous potential, the current study aimed to synthesize these derivatives in order to evaluate their biological properties against carbonic anhydrase II (CA-II) and Dickkopf - 1(Dkk1) protein which are highly expressed in many cancers including lung cancer. A series of 10 sulfanilamide derivatives was synthesized under controlled conditions using reflux condensation method. Among all the synthesized derivatives (5a-5j), the compound 5d was found to possess highest antioxidant activity (90.7397 ± 0.0732 µg/mL) comparable to vitamin C (95.1571 ± 0.057 µg/mL) and also exhibited maximum inhibition against CA-II with an IC(50) value of 0.00690 ± 0.1119 µM, indicating that 5d is significantly more potent as compared to standard i.e., acetazolamide IC(50) = 0.9979 ± 0.0024 µM. Keeping in view the importance of Dkk1 protein in cancer progression, the molecular docking investigations were performed, where compound 5d was proved to be the potential dual inhibitor of CA-II as well as Dkk1 with the binding energy of 8.9 and 9.7 kcal/mol, respectively. In addition to this DNA binding studies also confirmed the significance of compound 5d where it had maximum binding constant value of 6.7 × 10(4) mol(- 1), supporting the other biological investigations and was in agreement with the reported values. All the experimental and computational results reveals the excellent potential of 5d as a candidate medicine in future. Conclusively, the current study may lead to the new therapeutic strategies for the treatment of cancer associated with the aberrant expression of CA-II and less explored DDK1 target.