{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:27:59Z","timestamp":1790958479509,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSPD2023R852"],"award-info":[{"award-number":["RSPD2023R852"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In continuation of our research programs for the discovery, production, and development of the pharmacological activities of molecules for various disease treatments, Schiff bases and pyrazole scaffold have a broad spectrum of activities in biological applications. In this context, this manuscript aims to evaluate and study Schiff base\u2013pyrazole molecules as a new class of antioxidant (total antioxidant capacity, iron-reducing power, scavenging activity against DPPH, and ABTS radicals), anti-diabetic (\u03b1-amylase% inhibition), anti-Alzheimer\u2019s (acetylcholinesterase% inhibition), and anti-arthritic (protein denaturation% and proteinase enzyme% inhibitions) therapeutics. Therefore, the Schiff bases bearing pyrazole scaffold (22a, b and 23a, b) were designed and synthesized for evaluation of their antioxidant, anti-diabetic, anti-Alzheimer\u2019s, and anti-arthritic properties. The results for compound 22b demonstrated significant antioxidant, anti-diabetic (\u03b1-amylase% inhibition), and anti-Alzheimer\u2019s (ACE%) activities, while compound 23a demonstrated significant anti-arthritic activity. Prediction of in silico bioinformatics analysis (physicochemical properties, bioavailability radar, drug-likeness, and medicinal chemistry) of the target derivatives (22a, b and 23a, b) was performed. The molecular lipophilicity potential (MLP) of the derivatives 22a, b and 23a, b was measured to determine which parts of the surface are hydrophobic and which are hydrophilic. In addition, the molecular polar surface area (PSA) was measured to determine the polar surface area and the non-polar surface area of the derivatives 22a, b and 23a, b. This study could be useful to help pharmaceutical researchers discover a new series of potent agents that may act as an antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic.<\/jats:p>","DOI":"10.3390\/molecules28207125","type":"journal-article","created":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T08:25:09Z","timestamp":1697531109000},"page":"7125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["In Vitro Evaluation and Bioinformatics Analysis of Schiff Bases Bearing Pyrazole Scaffold as Bioactive Agents: Antioxidant, Anti-Diabetic, Anti-Alzheimer, and Anti-Arthritic"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6983-8587","authenticated-orcid":false,"given":"Hamad M.","family":"Alkahtani","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8711-3873","authenticated-orcid":false,"given":"Abdulrahman A.","family":"Almehizia","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9866-343X","authenticated-orcid":false,"given":"Mohamed A.","family":"Al-Omar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7532-6318","authenticated-orcid":false,"given":"Ahmad J.","family":"Obaidullah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4563-0351","authenticated-orcid":false,"given":"Amer A.","family":"Zen","sequence":"additional","affiliation":[{"name":"Chemistry & Forensics Department, Clifton Campus, Nottingham Trent University, Nottingham Ng11 8NS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4771-716X","authenticated-orcid":false,"given":"Ashraf S.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4848-0731","authenticated-orcid":false,"given":"Wael M.","family":"Aboulthana","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Biotechnology Research Institute, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,17]]},"reference":[{"key":"ref_1","first-page":"100188","article-title":"A review on potential anti-diabetic mechanisms of chitosan and its derivatives","volume":"3","author":"Priyanka","year":"2022","journal-title":"Carbohydr. Polym. Technol. Appl."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lima, E., and Medeiros, J. (2022). Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents. Mar. Drugs, 20.","DOI":"10.3390\/md20010075"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1016\/j.bmc.2015.05.010","article-title":"Anti-arthritic agents: Progress and potential","volume":"23","author":"Laev","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"214275","DOI":"10.1016\/j.ccr.2021.214275","article-title":"Chemical implications and considerations on techniques used to assess the in vitro antioxidant activity of coordination compounds","volume":"451","author":"Marchi","year":"2022","journal-title":"Coord. Chem. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2174\/1566524022666211222161637","article-title":"Free radicals and oxidative stress: Signaling mechanisms, redox basis for human diseases, and cell cycle regulation","volume":"23","author":"Sadiq","year":"2023","journal-title":"Curr. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jena, A.B., Samal, R.R., Bhol, N.K., and Duttaroy, A.K. (2023). Cellular Red-Ox system in health and disease: The latest update. Biomed. Pharmacother., 162.","DOI":"10.1016\/j.biopha.2023.114606"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14800","DOI":"10.1038\/s41598-023-41897-6","article-title":"Lipid metabolism transcriptomics of murine microglia in Alzheimer\u2019s disease and neuroinflammation","volume":"13","author":"Shippy","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s11030-022-10454-0","article-title":"Syntheses, in vitro, and in silico studies of rhodanine-based schiff bases as potential \u03b1-amylase inhibitors and radicals (DPPH and ABTS) scavengers","volume":"27","author":"Egu","year":"2022","journal-title":"Mol. Divers."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6818","DOI":"10.1080\/10406638.2021.1991392","article-title":"Synthesis, Spectral Characterization, Electronic Structure and Biological Activity Screening of the Schiff Base 4-((4-Hydroxy-3-Methoxy-5-Nitrobenzylidene) Amino)-N-(Pyrimidin-2-yl) Benzene Sulfonamide from 5-Nitrovaniline and Sulphadiazene","volume":"42","author":"Elangovan","year":"2022","journal-title":"Polycycl. Aromat. Compd."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"129666","DOI":"10.1016\/j.molstruc.2020.129666","article-title":"Synthesis, characterization, biological activity and molecular docking studies of novel schiff bases derived from thiosemicarbazide: Biochemical and computational approach","volume":"1231","author":"Taslimi","year":"2021","journal-title":"J. Mol. Struct."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"122450","DOI":"10.1016\/j.jorganchem.2022.122450","article-title":"Newly synthesized lanthanides complexes of ferrocene-based Schiff base with high biological activities and improved molecular docking data","volume":"977","author":"Sayed","year":"2022","journal-title":"J. Organomet. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"116448","DOI":"10.1016\/j.molliq.2021.116448","article-title":"Quasi liquid Schiff bases from trans-2-hexenal and cytosine and l-leucine with potential antieczematic and antiarthritic activities: Synthesis, structure and quantum mechanical studies","volume":"334","author":"Surendar","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Said, M.A., Khan, D.J., Al-Blewi, F.F., Al-Kaff, N.S., Ali, A.A., Rezki, N., Aouad, M.R., and Hagar, M. (2021). New 1, 2, 3-Triazole scaffold schiff bases as potential anti-COVID-19: Design, synthesis, DFT-molecular docking, and cytotoxicity aspects. Vaccines, 9.","DOI":"10.3390\/vaccines9091012"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e202203047","DOI":"10.1002\/slct.202203047","article-title":"Synthesis of Spiro-oxindole Analogs Engrafted Pyrazole Scaffold as Potential Alzheimer\u2019s Disease Therapeutics: Anti-oxidant, Enzyme Inhibitory and Molecular Docking Approaches","volume":"7","author":"Islam","year":"2022","journal-title":"ChemistrySelect"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20776","DOI":"10.1038\/s41598-021-99899-1","article-title":"Design, synthesis, biological evaluation, and molecular modeling studies of pyrazole-benzofuran hybrids as new \u03b1-glucosidase inhibitor","volume":"11","author":"Azimi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"113230","DOI":"10.1016\/j.ejmech.2021.113230","article-title":"Design, synthesis and biological evaluation of pyrazole-aromatic containing carboxamides as potent SDH inhibitors","volume":"214","author":"Yu","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"131591","DOI":"10.1016\/j.molstruc.2021.131591","article-title":"New Coumarin-Pyrazole hybrids: Synthesis, Docking studies and Biological evaluation as potential cholinesterase inhibitors","volume":"1249","author":"Chouh","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Signorello, M.G., Rapetti, F., Meta, E., Sidib\u00e8, A., Bruno, O., and Brullo, C. (2021). New series of pyrazoles and imidazo-pyrazoles targeting different cancer and inflammation pathways. Molecules, 26.","DOI":"10.3390\/molecules26195735"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"133843","DOI":"10.1016\/j.molstruc.2022.133843","article-title":"Synthesis, molecular docking and enzyme inhibitory approaches of some new chalcones engrafted pyrazole as potential antialzheimer, antidiabetic and antioxidant agents","volume":"1269","author":"Islam","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"458","DOI":"10.4172\/2161-0444.1000301","article-title":"Design, Synthesis. Vivo Anti-inflammatory, Analgesic Activities and Molecular Docking of Some Novel Pyrazolone Derivatives","volume":"5","author":"Eweas","year":"2015","journal-title":"Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Al-Ghorbani, M., Alharbi, O., Al-Odayni, A.B., and Abduh, N.A. (2023). Quinoline-and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of \u03b1-Glycosidase and \u03b1-Amylase Enzymes. Pharmaceuticals, 16.","DOI":"10.3390\/ph16091222"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"130520","DOI":"10.1016\/j.molstruc.2021.130520","article-title":"Antiproliferative properties and structural analysis of newly synthesized Schiff bases bearing pyrazole derivatives and molecular docking studies","volume":"1241","author":"Altunoglu","year":"2021","journal-title":"J. Mol. Struct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10137","DOI":"10.1007\/s11164-015-2018-1","article-title":"Design, synthesis, and antibacterial evaluation of new Schiff\u2019s base derivatives bearing nitroimidazole and pyrazole nuclei as potent E. coli FabH inhibitors","volume":"41","author":"Sangani","year":"2015","journal-title":"Res. Chem. Intermed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"112438","DOI":"10.1016\/j.ejmech.2020.112438","article-title":"Recent advancements in the development of heterocyclic anti-inflammatory agents","volume":"200","author":"Sharma","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100349","DOI":"10.1016\/j.mtchem.2020.100349","article-title":"Hydrazone comprising compounds as promising anti-infective agents: Chemistry and structure-property relationship","volume":"18","author":"Sharma","year":"2020","journal-title":"Mater. Today Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1120911","DOI":"10.3389\/fphar.2023.1120911","article-title":"LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials","volume":"14","author":"Noce","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.jsps.2023.04.003","article-title":"Bioinformatics and network pharmacology-based study to elucidate the multi-target pharmacological mechanism of the indigenous plants of Medina valley in treating HCV-related hepatocellular carcinoma","volume":"31","author":"Alamri","year":"2023","journal-title":"Saudi Pharm. J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Al-Wahaibi, L.H., Mohammed, A.F., Abdelrahman, M.H., Trembleau, L., and Youssif, B.G. (2023). Design, Synthesis, and Biological Evaluation of Indole-2-carboxamides as Potential Multi-Target Antiproliferative Agents. Pharmaceuticals, 16.","DOI":"10.3390\/ph16071039"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1080\/07391102.2022.2040593","article-title":"Discovery of multi-target mur enzymes inhibitors with anti-mycobacterial activity through a Scaffold approach","volume":"41","author":"Kumari","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"115180","DOI":"10.1016\/j.ejmech.2023.115180","article-title":"4-(5-Amino-pyrazol-1-yl) benzenesulfonamide derivatives as novel multi-target anti-inflammatory agents endowed with inhibitory activity against COX-2, 5-LOX and carbonic anhydrase: Design, synthesis, and biological assessments","volume":"250","author":"Ragab","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2174\/1568026623666230123142357","article-title":"Multi-target polypharmacology of 4-aminoquinoline compounds against malaria, tuberculosis and cancer","volume":"23","author":"Nandi","year":"2023","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1080\/17460441.2023.2214361","article-title":"Designing multi-target drugs for the treatment of major depressive disorder","volume":"18","author":"Halder","year":"2023","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"135616","DOI":"10.1016\/j.molstruc.2023.135616","article-title":"Recent Developments in the Synthesis of Hybrid Heterocycles, A Promising Approach to Develop Multi-target Antibacterial Agents","volume":"1286","author":"Sadek","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"114058","DOI":"10.1016\/j.ejmech.2021.114058","article-title":"Discovery of phthalazino [1,2-b]quinazolinone derivatives as multi-target HDAC inhibitors for the treatment of hepatocellular carcinoma via activating the p53 signal pathway","volume":"229","author":"Liu","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1007\/s13738-022-02551-6","article-title":"Antimicrobial evaluation, in silico ADMET prediction, molecular docking, and molecular electrostatic potential of pyrazole-isatin and pyrazole-indole hybrid molecules","volume":"19","author":"Hassan","year":"2022","journal-title":"J. Iran. Chem. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"135","DOI":"10.4314\/bcse.v33i1.13","article-title":"V2O5\/SiO2 as an efficient catalyst in the synthesis of 5-amino-pyrazole derivatives under solvent free condition","volume":"33","author":"Khatab","year":"2019","journal-title":"Bull. Chem. Soc. Ethiop."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s13738-021-02319-4","article-title":"Synthesis, molecular docking, and in silico ADME prediction of some fused pyrazolo [1,5-a]pyrimidine and pyrazole derivatives as potential antimicrobial agents","volume":"19","author":"Hassan","year":"2022","journal-title":"J. Iran. Chem. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.31557\/APJCP.2022.23.8.2671","article-title":"In vitro study on effect of zinc oxide nanoparticles on the biological activities of croton Tiglium L. Seeds extracts","volume":"23","author":"Aboulthana","year":"2022","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"59930","DOI":"10.1007\/s11356-022-20039-x","article-title":"In vitro antioxidant, anticancer, anti-inflammatory, anti-diabetic and anti-Alzheimer potentials of innovative macroalgae bio-capped silver nanoparticles","volume":"29","author":"Azeem","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"109274","DOI":"10.1016\/j.inoche.2022.109274","article-title":"Zingiber officinale driven bioproduction of ZnO nanoparticles and their anti-inflammatory, anti-diabetic, anti-Alzheimer, anti-oxidant, and anti-microbial applications","volume":"140","author":"Faisal","year":"2022","journal-title":"Inorg. Chem. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"W5","DOI":"10.1093\/nar\/gkab255","article-title":"ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties","volume":"49","author":"Xiong","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1021\/jm701122q","article-title":"Generation of a set of simple, interpretable ADMET rules of thumb","volume":"51","author":"Gleeson","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1016\/j.bmcl.2008.07.071","article-title":"Physiochemical drug properties associated with in vivo toxicological outcomes","volume":"18","author":"Hughes","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1758-2946-1-8","article-title":"Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions","volume":"1","author":"Ertl","year":"2009","journal-title":"J. Cheminform."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1021\/ci700286x","article-title":"Natural product-likeness score and its application for prioritization of compound libraries","volume":"48","author":"Ertl","year":"2008","journal-title":"J. Chem. Inf. Model"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s13765-014-4201-2","article-title":"Antibacterial and cytotoxic activities of Schiff base analogues of 4-aminoantipyrine","volume":"57","author":"Alam","year":"2014","journal-title":"J. Korean Soc. Appl. Biol. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/20\/7125\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:08:20Z","timestamp":1760130500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/20\/7125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,17]]},"references-count":48,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["molecules28207125"],"URL":"https:\/\/doi.org\/10.3390\/molecules28207125","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,17]]}}}