Antitumor activity, X-Ray crystallography, in silico study of some-sulfamido-phosphonates. Identification of pharmacophore sites

•Eight novel highly functionalized sulfamido-phosphonates were evaluated for their in vitro antitumor activity.•Molecular docking study was performed in order to evaluate synthesized compounds as possible inhibitors of human carbonic anhydrase I•The physicochemical properties of sulfamido-phosphonates has been optimized using bioinformatics studies•POM analyses identify other interesting pharmacophore sites of compounds 3a-3h.•A single crystal of the studied compound 3h, were selected for single crystal X-ray diffraction analysis. The key compounds, sulfamidophosphonate derivatives 3a–3h, were evaluated in vitro for their antitumor activity against three cancer cell lines Jurkat (acute T cell Leukaemia, ATCC TIB-152), K562 (chronic myelogenous leukaemia, ATCC CLL-243) and PRI (LCL, Lymphoblastic Cell Lines). Molecular docking study was performed in order to evaluate synthesized compounds as possible inhibitors of human carbonic anhydrase I and their interactions in binding sites. Key interactions of the most potentially active compound are the hydrogen bond with the Gln92, His119, Thr199 and His200. Phenyl rings and nitrogen atoms of sulfonyl moiety generate numerous aromatics and van der Waals interactions, mainly with His 200, His94, Lue198, and Gln92. Compound 3h crystallizes in the triclinic crystal system (space group P-1). The bioinformatic POM/DFT analyses confirm the existence of other interesting pharmacophore sites. [Display omitted]