{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T09:16:09Z","timestamp":1764494169145,"version":"3.37.3"},"reference-count":24,"publisher":"International Union of Crystallography (IUCr)","issue":"8","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html#TDM"}],"funder":[{"DOI":"10.13039\/501100014410","name":"Pedagogical University of Krakow","doi-asserted-by":"crossref","award":["BN.610-185\/PBU\/2020"],"award-info":[{"award-number":["BN.610-185\/PBU\/2020"]}],"id":[{"id":"10.13039\/501100014410","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["Acta Crystallogr C Struct Chem","Acta Crystallogr C","Acta Crystallogr C Cryst Struct Commun","Acta Cryst C","Acta Cryst C Struct Chem","Acta Cryst Sect C","Acta Cryst Sect C Struct Chem","Acta Crystallogr Sect C","Acta Crystallogr Sect C Struct Chem","Acta Crystallogr Sect C Cryst Struct Commun"],"accepted":{"date-parts":[[2021,6,28]]},"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:p>5-Spirofluorenehydantoin derivatives show efflux modulating, cytotoxic and antiproliferative effects in sensitive and resistant mouse T-lymphoma cells. In order to extend the knowledge available about the pharmacophoric features responsible for the glycoprotein P (P-gp) inhibitory properties of arylpiperazine derivatives of 3-methyl-5-spirofluorenehydantoin, we have performed crystal structure analyses for 1-[3-(3\u2032-methyl-2\u2032,4\u2032-dioxospiro[fluorene-9,5\u2032-imidazolidin]-1\u2032-yl)propyl]-4-phenylpiperazine-1,4-diium dichloride monohydrate, C<jats:sub>29<\/jats:sub>H<jats:sub>32<\/jats:sub>N<jats:sub>4<\/jats:sub>O<jats:sub>2<\/jats:sub>\n                  <jats:sup>2+<\/jats:sup>\u00b72Cl<jats:sup>\u2212<\/jats:sup>\u00b7H<jats:sub>2<\/jats:sub>O (<jats:bold>1<\/jats:bold>), 3\u2032-methyl-1\u2032-{3-[4-(4-nitrophenyl)piperazin-1-yl]propyl}spiro[fluorene-9,5\u2032-imidazolidine]-2\u2032,4\u2032-dione, C<jats:sub>29<\/jats:sub>H<jats:sub>29<\/jats:sub>N<jats:sub>5<\/jats:sub>O<jats:sub>4<\/jats:sub>\u00b7H<jats:sub>2<\/jats:sub>O (<jats:bold>2<\/jats:bold>), 3\u2032-methyl-1\u2032-{5-[4-(4-nitrophenyl)piperazin-1-yl]pentyl}spiro[fluorene-9,5\u2032-imidazolidine]-2\u2032,4\u2032-dione, C<jats:sub>31<\/jats:sub>H<jats:sub>33<\/jats:sub>N<jats:sub>5<\/jats:sub>O<jats:sub>4<\/jats:sub> (<jats:bold>3<\/jats:bold>), and 1-benzyl-4-[5-(3\u2032-methyl-2\u2032,4\u2032-dioxospiro[fluorene-9,5\u2032-imidazolidin]-1\u2032-yl)pentyl]piperazine-1,4-diium dichloride 0.613-hydrate, C<jats:sub>32<\/jats:sub>H<jats:sub>38<\/jats:sub>N<jats:sub>4<\/jats:sub>O<jats:sub>2<\/jats:sub>\n                  <jats:sup>2+<\/jats:sup>\u00b72Cl<jats:sup>\u2212<\/jats:sup>\u00b70.613H<jats:sub>2<\/jats:sub>O (<jats:bold>4<\/jats:bold>). Structure <jats:bold>3<\/jats:bold> is anhydrous but the other three structures crystallize with water present. The investigated compounds crystallize in the monoclinic crystal system, with the space group <jats:italic>P<\/jats:italic>2<jats:sub>1<\/jats:sub>\/<jats:italic>n<\/jats:italic> for <jats:bold>1<\/jats:bold> and <jats:bold>3<\/jats:bold>, and <jats:italic>P<\/jats:italic>2<jats:sub>1<\/jats:sub>\/<jats:italic>c<\/jats:italic> for <jats:bold>2<\/jats:bold> and <jats:bold>4<\/jats:bold>. The cations of salts <jats:bold>1<\/jats:bold> and <jats:bold>4<\/jats:bold> are doubly protonated, with the protons located on the N atoms of the piperazine rings. The packing of <jats:bold>1<\/jats:bold> and <jats:bold>4<\/jats:bold> in the crystals is dominated by intermolecular N\u2014H...Cl and O\u2014H...Cl hydrogen bonds. In the crystal structure of <jats:bold>2<\/jats:bold>, the intermolecular interactions are dominated by O\u2014H...O and O\u2014H...N hydrogen bonds, while in <jats:bold>3<\/jats:bold>, which is lacking in classic hydrogen-bond donors, it is C\u2014H...O contacts that dominate. Additionally, we have performed induced-fit docking studies for the investigated compounds docked to the P-gp human homology model.<\/jats:p>","DOI":"10.1107\/s2053229621006756","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T09:59:40Z","timestamp":1625738380000},"page":"467-478","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":5,"title":["Crystallographic studies of piperazine derivatives of 3-methyl-5-spirofluorenehydantoin in search of structural features of P-gp inhibitors"],"prefix":"10.1107","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-9370","authenticated-orcid":true,"given":"Ewa","family":"\u017bes\u0142awska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3025-7002","authenticated-orcid":true,"given":"Ewa","family":"Szyma\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Nitek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jadwiga","family":"Handzlik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"329","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"ky3205_bb1","doi-asserted-by":"crossref","first-page":"112435","DOI":"10.1016\/j.ejmech.2020.112435","volume":"200","author":"Ali","year":"2020","journal-title":"Eur. 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