Computer-Aided Drug Design tools are now an indispensable part of drug discovery that have made key contributions to the development of drugs. In this editorial, I briefly provide an overview of CADD emphasizing its potential and invite authors from academia and the pharmaceutical and biotechnology sector to present their research in this collection.

In this study, a library of twelve beta-lactam-substituted benzenesulfonamides (5a-l) was synthesized using the tail-approach method. The compounds were characterized using IR, ¹H NMR, ¹³C NMR and elemental analysis techniques. These newly synthesized compounds were tested for their ability to inhibit the activity of two carbonic anhydrases (hCA) isoforms, I and II, and acetylcholinesterase (AChE) in vitro. The results showed that the synthesized compounds were potent inhibitors of hCA I, with K_Is in the low nanomolar range (66.60-278.40 nM) than the reference drug acetazolamide (AAZ), which had a K_I of 439.17 nM. The hCA II was potently inhibited by compounds 5a, 5d-g and 5l, with K_Is of 69.56, 39.64, 79.63, 74.76, 78.93 and 74.94 nM, respectively (AAZ, K_I of 98.28 nM). Notably, compound 5a selectively inhibited hCA II with a selectivity of > 4-fold over hCA I. In terms of inhibition of AChE, the synthesized compounds had K_Is ranging from 30.95 to 154.50 nM, compared to the reference drug tacrine, which had a K_I of 159.61 nM. Compounds 5f, 5h and 5l were also evaluated for their ability to inhibit the MCF-7 cancer cell line proliferation and were found to have promising anticancer activity, more potent than 5-fluorouracil and cisplatin. Molecular docking studies suggested that the sulfonamide moiety of these compounds fits snugly into the active sites of hCAs and interacts with the Zn²⁺ ion. Furthermore, molecular dynamics simulations were performed for 200 ns to assess the stability and dynamics of each enzyme-ligand complex. The acceptability of the compounds based on Lipinski's and Jorgensen's rules was also estimated from the ADME/T results. These results indicate that the synthesized molecules have the potential to be developed into effective and safe inhibitors of hCAs and AChE and could be lead agents.Communicated by Ramaswamy H. Sarma.