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Combined DFT and molecular docking studies of synthesized steroidal lactams reveal their potential as aromatase inhibitors.

The C(4) N‐heteroaryl 2‐amino‐3‐nitro‐4H‐chromenes are podophyllotoxin (POD) mimics as they possess the pharmacophore features of the anticancer natural product. We have achieved a facile synthesis of several such 4H‐chromenes by substitution of C(4) SMe in N‐alkyl 4‐(methylthio)‐3‐nitro‐4H‐chromen‐2‐amines with heteroaromatic amines like 2‐aminopyridines and 2‐aminopyrimidines. Resulting 4H‐chromenes were evaluated for anticancer activity against prostate and lung cancer cell lines. Two of the 4H‐chromenes showed significant anti‐cancer activity, even better than POD. Both of them were non‐toxic towards normal cell‐lines. In silico ADMET studies revealed drug‐likeliness of all the 4H‐chromenes. Molecular docking studies with αβ tubulin concurred with in vivo results and revealed that the 4H‐chromenes bind to the active site of POD. Molecular dynamics simulation studies on the complexes of αβ tubulin with the two best 4H‐chromenes revealed high stability. Overall, our studies revealed that the two 4H‐chromenes could act as lead compounds for further development of potent anticancer drugs.

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