{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:26:44Z","timestamp":1790036804165,"version":"4.0.1"},"reference-count":20,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation","award":["451-03-137\/2025-03\/200134"],"award-info":[{"award-number":["451-03-137\/2025-03\/200134"]}]},{"name":"Ministry of Science, Technological Development and Innovation","award":["451-03-137\/2025-03\/200125"],"award-info":[{"award-number":["451-03-137\/2025-03\/200125"]}]},{"name":"Ministry of Science, Technological Development and Innovation","award":["451-03-136\/2025-03\/200125"],"award-info":[{"award-number":["451-03-136\/2025-03\/200125"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Previously reported analyses show that some androstane-3-oxime derivatives with picolyl and picolinylidene functional groups possess a significant anticancer activity towards various cancer cell lines. These findings suggest that these compounds have prominent biological potential and represent a good basis for further research. The present study aims to determine their anisotropic lipophilicity as a physicochemical parameter relevant to both prediction of chromatographic behavior and biological activity. Methods: Anisotropic lipophilicity was determined using reversed-phase ultra-high performance liquid chromatography (RP-UHPLC) systems equipped with three stationary phases (C18, C8 and phenyl) and three mobile phases composed of water with different modifiers (methanol, acetonitrile and a methanol-acetonitrile mixture). Capacity factors (logk) were obtained for all compounds across the chromatographic systems to describe their behavior in anisotropic environments. Chemometric analyses were performed using linear pattern recognition techniques (PRT), such as hierarchical cluster analysis (HCA) and principal component analysis (PCA), and non-linear clustering based on artificial neural networks (CANN). Results: The experimentally determined chromatographic parameters were correlated with in silico lipophilicity values (logP). This comparison allowed for examination of the concordance between experimental and computed data for the series of androstanes. The chemometric analysis resulted in models that provided an overview of the grouping of compounds in the space of the determined chromatographic parameters. Conclusions: The results demonstrate strong agreement between experimental and computational lipophilicity parameters. This very good data fit provides a reliable foundation for further studies exploring the relationships between lipophilicity and biological activity of the studied androstane derivatives.<\/jats:p>","DOI":"10.3390\/ph18121778","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:24:17Z","timestamp":1763979857000},"page":"1778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comprehensive Chemometric and Chromatographic Investigation of Lipophilicity of Biologically Active Androstane-3-Oxime Derivatives Across Diverse UHPLC Systems"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5619-9894","authenticated-orcid":false,"given":"Strahinja Z.","family":"Kova\u010devi\u0107","sequence":"first","affiliation":[{"name":"Department of Applied and Engineering Chemistry, Faculty of Technology Novi Sad, University of Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0514-4033","authenticated-orcid":false,"given":"Milica \u017d.","family":"Karad\u017ei\u0107 Banjac","sequence":"additional","affiliation":[{"name":"Department of Applied and Engineering Chemistry, Faculty of Technology Novi Sad, University of Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4269-9206","authenticated-orcid":false,"given":"Sanja O.","family":"Podunavac-Kuzmanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Applied and Engineering Chemistry, Faculty of Technology Novi Sad, University of Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2750-1994","authenticated-orcid":false,"given":"Jasmina S.","family":"Anoj\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovi\u0107a 3, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0218-3640","authenticated-orcid":false,"given":"Jovana J.","family":"Ajdukovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovi\u0107a 3, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Huo, S., Wu, J., He, X., Pan, L., and Du, J. (2019). Two New Cytotoxic Steroidal Alkaloids from Sarcococca Hookeriana. Molecules, 24.","DOI":"10.3390\/molecules24010011"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104604","DOI":"10.1016\/j.fitote.2020.104604","article-title":"Cytotoxic androstane derivatives from Sarcococca ruscifolia","volume":"144","author":"Yi","year":"2020","journal-title":"Fitoterapia"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mustafa, N.H., Sekar, M., Fuloria, S., Begum, M.Y., Gan, S.H., Rani, N.N.I.M., Ravi, S., Chidambaram, K., Subramaniyan, V., and Sathasivam, K.V. (2022). Chemistry, Biosynthesis and Pharmacology of Sarsasapogenin: A Potential Natural Steroid Molecule for New Drug Design, Development and Therapy. Molecules, 27.","DOI":"10.3390\/molecules27062032"},{"key":"ref_4","first-page":"102236","article-title":"\u03b2-Ecdysterone and Sarsasapogenin, first isolated from Polygonatum kingianum, reveal its therapeutic potential in MAFLD via 16S rRNA sequencing and metabolomics","volume":"23","author":"Zhou","year":"2025","journal-title":"J. Agric. Food Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"An, R.F., Wu, K.T., Pan, J., Zhang, W.J., Qin, H.Y., Li, X.R., Liu, W., and Huang, X.F. (2025). Design, synthesis and cytotoxic activity of novel lipophilic cationic derivatives of diosgenin and sarsasapogenin. Bioorganic Med. Chem. Lett., 119.","DOI":"10.1016\/j.bmcl.2025.130094"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7257","DOI":"10.1016\/j.bmc.2013.09.063","article-title":"17(E)-picolinylidene androstane derivatives as potential inhibitors of prostate cancer cell growth: Antiproliferative activity and molecular docking studies","volume":"21","author":"Petri","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dzichenka, Y., Shapira, M., Yantsevich, A., Cherkesova, T., Grbovi\u0107, L., Savi\u0107, M., Usanov, S., and Jovanovi\u0107-\u0160anta, S. (2021). Modified bile acids and androstanes-Novel promising inhibitors of human cytochrome P450 17A1. J. Steroid Biochem. Mol. Biol., 205.","DOI":"10.1016\/j.jsbmb.2020.105777"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"117850","DOI":"10.1016\/j.ejmech.2025.117850","article-title":"Heterocyclic androstane derivatives targeting hormone-related cancers: Synthesis, bioactivity and docking studies","volume":"296","author":"Petri","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.steroids.2016.02.011","article-title":"Synthesis of 5\u03b1-androstane-3\u03b1,17\u03b2-diol 17-O-glucuronide histaminyl conjugate for immunoassays","volume":"109","year":"2016","journal-title":"Steroids"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108596","DOI":"10.1016\/j.steroids.2020.108596","article-title":"New A-homo lactam D-homo lactone androstane derivative: Synthesis and evaluation of cytotoxic and anti-inflammatory activities in vitro","volume":"157","author":"Kuzminac","year":"2020","journal-title":"Steroids"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kulm\u00e1ny, \u00c1.E., Herman, B.E., Zupk\u00f3, I., Sinreih, M., Ri\u017ener, T.L., Savi\u0107, M., Oklje\u0161a, A., Nikoli\u0107, A., Nagy, V., and Ocsovszki, I. (2021). Heterocyclic androstane and estrane d-ring modified steroids: Microwave-assisted synthesis, steroid-converting enzyme inhibition, apoptosis induction, and effects on genes encoding estrogen inactivating enzymes. J. Steroid Biochem. Mol. Biol., 214.","DOI":"10.1016\/j.jsbmb.2021.105997"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37449","DOI":"10.1039\/D1RA07613B","article-title":"Novel alkylaminoethyl derivatives of androstane 3-oximes as anticancer candidates: Synthesis and evaluation of cytotoxic effect","volume":"11","author":"Jakimov","year":"2021","journal-title":"RSC Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejps.2016.07.008","article-title":"Comprehensive QSRR modeling as a starting point in characterization and further development of anticancer drugs based on 17\u03b1-picolyl and 17(E)-picolinylidene androstane structures","volume":"93","author":"Jovanov","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"463197","DOI":"10.1016\/j.chroma.2022.463197","article-title":"Chemometrics of anisotropic lipophilicity of anticancer androstane derivatives determined by reversed-phase ultra high performance liquid chromatography with polar aprotic and protic modifiers","volume":"1673","author":"Kuzminac","year":"2022","journal-title":"J. Chromatogr. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"464549","DOI":"10.1016\/j.chroma.2023.464549","article-title":"Modeling of small molecule\u2019s affinity to phospholipids using IAM-HPLC and QSRR approach enhanced by similarity-based machine algorithms","volume":"1714","author":"Ciura","year":"2024","journal-title":"J. Chromatogr. A"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1021\/cr068412z","article-title":"QSRR: Quantitative Structure-(Chromatographic) Retention Relationship","volume":"107","author":"Kaliszan","year":"2007","journal-title":"Chem. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"135272","DOI":"10.1016\/j.molstruc.2023.135272","article-title":"Local QSAR modeling of cytotoxic activity of newly designed androstane 3-oximes towards malignant melanoma cells","volume":"1283","author":"Ivanov","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1080\/10826070802279202","article-title":"Characterization of the GEMINI C18TM Column: Lipophilicity Measurement and LSER","volume":"31","author":"Benhaim","year":"2008","journal-title":"J. Liq. Chromatogr. Relat. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"464974","DOI":"10.1016\/j.chroma.2024.464974","article-title":"Preparation and characterization of stationary phase gradients on C8 liquid chromatography columns","volume":"1727","author":"Cecil","year":"2024","journal-title":"J. Chromatogr. A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"381","DOI":"10.2174\/0929867033368268","article-title":"Chromatographic Retention Parameters in Medicinal Chemistry and Molecular Pharmacology","volume":"10","author":"Nasal","year":"2003","journal-title":"Curr. Med. Chem."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1778\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:29:19Z","timestamp":1763980159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,23]]},"references-count":20,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ph18121778"],"URL":"https:\/\/doi.org\/10.3390\/ph18121778","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,23]]}}}