{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:01:32Z","timestamp":1790017292912,"version":"4.0.1"},"reference-count":70,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Nourah bint Abdulrahman University Researchers Supporting Project","award":["PNURSP2025R304"],"award-info":[{"award-number":["PNURSP2025R304"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Type 2 diabetes mellitus (T2DM) presents a significant global health challenge, with obesity being a major contributing risk factor alongside genetic and non-genetic elements. Current treatments focus on reducing hyperglycemia and preventing T2DM progression, often involving drug combinations for enhanced efficacy. This study introduces two novel nitrogen-containing heterocyclic scaffolds: neocryptolepine\u2013thiazolidinedione (NC-TZD) 8 and acridine\u2013thiazolidinedione (AC-TZD) 11. Methods: These compounds were synthesized and characterized using various spectroscopic techniques. Their antihyperglycemic and antihyperlipidemic effects were assessed in an obesity-induced zebrafish model. Hyperglycemia was induced by immersing zebrafish in 100 mM glucose monohydrate for two weeks. Fish were then divided into groups receiving either 20 mg or 80 mg of the drugs per kg of body weight, alongside negative and positive control groups. Results: Both doses of hybrids 8 and 11 effectively restored glucose, triglyceride, insulin, and nuclear factor kappa beta (nf\u03ba\u03b2) mRNA levels to normal. However, only the lower doses restored peroxisomal acyl-CoA oxidase (acox1) mRNA levels, with higher doses proving less effective. A molecular modeling study supported the antidiabetic potential of hybrids 8 and 11, suggesting interactions with target proteins PPAR-\u03b1 and acox1. In silico ADMET analysis revealed promising oral bioavailability and drug likeness for both compounds. Conclusions: The findings indicate that both hybrids exhibit significant antihyperglycemic and antihypertriglyceridemic effects, particularly at lower doses. These results highlight the promising therapeutic potential of these novel oral bioavailable compounds in managing T2DM. Further research is warranted to elucidate their mechanisms of action.<\/jats:p>","DOI":"10.3390\/ph18071023","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:38:27Z","timestamp":1752140307000},"page":"1023","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In Vivo Antidiabetic and Antilipidemic Effect of Thiazolidine-2,4-Dione Linked Heterocyclic Scaffolds in Obesity-Induced Zebrafish Model"],"prefix":"10.3390","volume":"18","author":[{"given":"Asmaa","family":"Galal-Khallaf","sequence":"first","affiliation":[{"name":"Zoology Department, Faculty of Science, Menoufia University, Shebin EL-Kom P.O. Box 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawlat","family":"Mousa","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom P.O. Box 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aml","family":"Atyah","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom P.O. Box 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Bahnsawye","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom P.O. Box 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona K. Abo","family":"Hussein","sequence":"additional","affiliation":[{"name":"Clinical Microbiology and Immunology Department, National Liver Institute, Menoufia University, Shebin El-Kom P.O. Box 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1227-7931","authenticated-orcid":false,"given":"Ibrahim El Tantawy","family":"El Sayed","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom P.O. Box 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1160-5040","authenticated-orcid":false,"given":"Elshaymaa I.","family":"Elmongy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo P.O. Box 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1406-282X","authenticated-orcid":false,"given":"Reem","family":"Binsuwaidan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel Moneim A. K.","family":"El-Torgoman","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom P.O. Box 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed","family":"Abdel-Bary","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom P.O. Box 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0281-816X","authenticated-orcid":false,"given":"Khaled","family":"Mohammed-Geba","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science, Menoufia University, Shebin EL-Kom P.O. Box 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ali, M.K., Galaviz, K.I., Weber, M.B., and Narayan, K.V. (2017). The global burden of diabetes. Textbook of Diabetes, Wiley.","DOI":"10.1002\/9781118924853.ch5"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zorena, K., Michalska, M., Kurpas, M., Jaskulak, M., Murawska, A., and Rostami, S. (2022). Environmental factors and the risk of developing type 1 diabetes\u2014Old disease and new data. Biology, 11.","DOI":"10.3390\/biology11040608"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/jdi.13155","article-title":"Pancreatic \u03b2-cells express major histocompatibility complex class II: Do diabetic \u03b2-cells have the capacity of antigen-presenting cells?","volume":"11","author":"Sano","year":"2019","journal-title":"J. Diabetes Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41574-020-0325-0","article-title":"Insights into pancreatic islet cell dysfunction from type 2 diabetes mellitus genetics","volume":"16","author":"Krentz","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1007\/s00125-020-05140-5","article-title":"Obesity, unfavourable lifestyle and genetic risk of type 2 diabetes: A case-cohort study","volume":"63","author":"Schnurr","year":"2020","journal-title":"Diabetologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e142243","DOI":"10.1172\/JCI142243","article-title":"Pharmacological treatment of hyperglycemia in type 2 diabetes","volume":"131","author":"Taylor","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_8","first-page":"442","article-title":"Type 2 diabetes and its impact on the immune system","volume":"16","author":"Berbudi","year":"2020","journal-title":"Curr. Diabetes Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1111\/jdi.13070","article-title":"Hyperglycemia in non-obese patients with type 2 diabetes is associated with low muscle mass: The Multicenter Study for Clarifying Evidence for Sarcopenia in Patients with Diabetes Mellitus","volume":"10","author":"Sugimoto","year":"2019","journal-title":"J. Diabetes Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"487","DOI":"10.2337\/dci19-0066","article-title":"2019 update to: Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"43","author":"Buse","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s00210-022-02302-7","article-title":"Unravelling the pharmacological properties of cryptolepine and its derivatives: A mini-review insight","volume":"396","author":"Tudu","year":"2023","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, N., \u015awitalska, M., Wang, L., Shaban, E., Hossain, M.I., El Sayed, I.E., Wietrzyk, J., and Inokuchi, T. (2019). Structural modifications of nature-inspired indoloquinolines: A mini review of their potential antiproliferative activity. Molecules, 24.","DOI":"10.3390\/molecules24112121"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Abd Elrahman, S.F., Ahmed, A.A., Abd Elsatar, D., Elkady, S., Elgendy, A., Alnakeeb, F., Elmongy, E.I., Henidi, H.A., El-Gendy, S.M., and El Sayed, I.E. (2023). Cytotoxic Potential of Novel Quinoline Derivative: 11-(1,4-Bisaminopropylpiperazinyl)5-methyl-5H-indolo[2,3-b]quinoline against Different Cancer Cell Lines via Activation and Deactivation of the Expression of Some Proteins. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814336"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s10495-023-01810-y","article-title":"Design and cytotoxic evaluation via apoptotic and antiproliferative activity for novel 11 (4-aminophenylamino) neocryptolepine on hepatocellular and colorectal cancer cells","volume":"28","author":"Nagy","year":"2023","journal-title":"Apoptosis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1021\/jm970735n","article-title":"Antihyperglycemic activities of cryptolepine analogues: An ethnobotanical lead structure isolated from Cryptolepis sanguinolenta","volume":"41","author":"Bierer","year":"1998","journal-title":"J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1039\/D4MD00199K","article-title":"Thiazolidine-2, 4-dione hybrids as dual alpha-amylase and alpha-glucosidase inhibitors: Design, synthesis, in vitro and in vivo anti-diabetic evaluation","volume":"15","author":"Singh","year":"2024","journal-title":"RSC Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"116589","DOI":"10.1016\/j.ejmech.2024.116589","article-title":"Discovery of new anti-diabetic potential agents based on paracetamol incorporating sulfa-drugs: Design, synthesis, \u03b1-amylase, and \u03b1-glucosidase inhibitors with molecular docking simulation","volume":"275","author":"Thabet","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s40995-018-0593-x","article-title":"Synthesis of new thiazolidine-2,-4-dione-azole derivatives and evaluation of their \u03b1-amylase and \u03b1-glucosidase inhibitory activity","volume":"43","author":"Senthilkumar","year":"2019","journal-title":"Iran. J. Sci. Technol. Trans. A Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.jare.2020.01.008","article-title":"An overview on medicinal perspective of thiazolidine-2, 4-dione: A remarkable scaffold in the treatment of type 2 diabetes","volume":"23","author":"Bansal","year":"2020","journal-title":"J. Adv. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1111\/cbdd.13017","article-title":"Design and synthesis of some acridine-piperazine hybrids for the improvement of cognitive dysfunction","volume":"90","author":"Sharma","year":"2017","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"El-Zahabi, M.A., Bamanie, F.H., Ghareeb, S., Alshaeri, H.K., Alasmari, M.M., Moustafa, M., Al-Marzooki, Z., and Zayed, M.F. (2022). Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of quinazoline-sulfonylurea hybrids as peroxisome proliferator-activated receptor gamma (PPAR\u03b3) and sulfonylurea receptor (SUR) agonists. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179605"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Patil, S., Alegaon, S.G., Gharge, S., Ranade, S.D., and Khatib, N.A. (2024). Molecular hybridization, synthesis, in vitro \u03b1-glucosidase inhibition, in vivo antidiabetic activity and computational studies of isatin based compounds. Bioorg. Chem., 153.","DOI":"10.1016\/j.bioorg.2024.107783"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1055\/s-0032-1304565","article-title":"Zebrafish: A Model for Understanding Diabetic Complications","volume":"120","author":"Hillebrands","year":"2012","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1080\/14756366.2017.1387543","article-title":"Synthesis and in vitro antiproliferative and antibacterial activity of new thiazolidine-2, 4-dione derivatives","volume":"33","author":"Trotsko","year":"2018","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dahlgren, D., and Lennern\u00e4s, H. (2019). Intestinal permeability and drug absorption: Predictive experimental, computational and in vivo approaches. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11080411"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Han, Y., Zhang, J., Hu, C.Q., Zhang, X., Ma, B., and Zhang, P. (2019). In silico ADME and toxicity prediction of ceftazidime and its impurities. Front. Pharmacol, 10.","DOI":"10.3389\/fphar.2019.00434"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"El-Tantawy, A.I., Elmongy, E.I., Elsaeed, S.M., Abdel Aleem, A.A.H., Binsuwaidan, R., Eisa, W.H., Salman, A.U., Elharony, N.E., and Attia, N.F. (2023). Synthesis, Characterization, and Docking Study of Novel Thioureidophosphonate-Incorporated Silver Nanocomposites as Potent Antibacterial Agents. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061666"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1021\/jm000942e","article-title":"Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-Based Contributions and Its Application to the Prediction of Drug Transport Properties","volume":"43","author":"Ertl","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1210\/jc.2005-2327","article-title":"Increased activation of nuclear factor \u03baB triggers inflammation and insulin resistance in polycystic ovary syndrome","volume":"91","author":"Rote","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ta\u00efl\u00e9, J., Patch\u00e9, J., Veeren, B., and Gonthier, M.P. (2021). Hyperglycemic condition causes pro-inflammatory and permeability alterations associated with monocyte recruitment and deregulated nf\u03bab\/ppar\u03b3 pathways on cerebral endothelial cells: Evidence for polyphenols uptake and protective effect. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031385"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"dmm036004","DOI":"10.1242\/dmm.036004","article-title":"Modelling pancreatic \u03b2-cell inflammation in zebrafish identifies the natural product wedelolactone for human islet protection","volume":"12","author":"Tsakmaki","year":"2019","journal-title":"Dis. Models Mech."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"855","DOI":"10.2337\/diabetes.48.4.855","article-title":"Hyperglycemia-induced activation of nuclear transcription factor kappaB in vascular smooth muscle cells","volume":"48","author":"Yerneni","year":"1999","journal-title":"Diabetes"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Behl, T., Gupta, A., Albratty, M., Najmi, A., Meraya, A.M., Alhazmi, H.A., Anwer, M.K., Bhatia, S., and Bungau, S.G. (2022). Alkaloidal phytoconstituents for diabetes management: Exploring the unrevealed potential. Molecules, 27.","DOI":"10.3390\/molecules27185851"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jayaraman, S., Devarajan, N., Rajagopal, P., Babu, S., Ganesan, S.K., Veeraraghavan, V.P., Palanisamy, C.P., Cui, B., Periyasamy, V., and Chandrasekar, K. (2021). \u03b2-Sitosterol circumvents obesity induced inflammation and insulin resistance by down-regulating IKK\u03b2\/NF-\u03baB and JNK signaling pathway in adipocytes of type 2 diabetic rats. Molecules, 26.","DOI":"10.3390\/molecules26072101"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.bmc.2006.10.018","article-title":"Synthetic cryptolepine inhibits DNA binding of NF-\u03baB","volume":"15","author":"Olajide","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"263","DOI":"10.5455\/jice.20160606124435","article-title":"Cryptolepine, an indoloquinoline alkaloid, in the management of diabetes mellitus and its associated complications","volume":"5","author":"Ameyaw","year":"2016","journal-title":"J. Intercult. Ethnopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"138311","DOI":"10.1016\/j.molstruc.2024.138311","article-title":"Synthesis, anti-\u03b1-glucosidase activity, inhibition interaction, and anti-diabetic activity of novel cryptolepine derivatives","volume":"1310","author":"Feng","year":"2024","journal-title":"J. Mol. Struct."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"120437","DOI":"10.1016\/j.jlumin.2024.120437","article-title":"Investigation on the inhibition mechanism and binding behavior of cryptolepine to \u03b1-glucosidase and its hypoglycemic activity by multi-spectroscopic method","volume":"269","author":"Min","year":"2024","journal-title":"J. Lumin."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, J., Zhang, R., Li, W., Ma, X.C., Qiu, F., and Sun, C.P. (2023). I\u03baB kinase \u03b2 (IKK\u03b2): Structure, transduction mechanism, biological function, and discovery of its inhibitors. Int. J. Biol. Sci., 19.","DOI":"10.7150\/ijbs.85158"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Li, M., Sun, J., Liang, B., Min, X., Hu, J., Wu, R., and Xu, X. (2024). Thiazolidine-2, 4-dione derivatives as potential \u03b1-glucosidase inhibitors: Synthesis, inhibitory activity, binding interaction and hypoglycemic activity. Bioorg. Chem., 144.","DOI":"10.1016\/j.bioorg.2024.107177"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1080\/07391102.2023.2291158","article-title":"Design, synthesis, biological evaluations and in silico studies of N-substituted 2, 4-thiazolidinedione derivatives as potential a-glucosidase inhibitors","volume":"43","author":"Dahiya","year":"2025","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gummidi, L., Kerru, N., Ebenezer, O., Awolade, P., Sanni, O., Islam, M.S., and Singh, P. (2021). Multicomponent reaction for the synthesis of new 1, 3, 4-thiadiazole-thiazolidine-4-one molecular hybrids as promising antidiabetic agents through \u03b1-glucosidase and \u03b1-amylase inhibition. Bioorg. Chem., 115.","DOI":"10.1016\/j.bioorg.2021.105210"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Khan, S., Iqbal, S., Khan, M., Rehman, W., Shah, M., Hussain, R., Rasheed, L., Khan, Y., Dera, A.A., and Pashameah, R.A. (2022). Design, synthesis, in silico testing, and in vitro evaluation of thiazolidinone-based benzothiazole derivatives as inhibitors of \u03b1-amylase and \u03b1-glucosidase. Pharmaceuticals, 15.","DOI":"10.3390\/ph15101164"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1271\/bbb.61.1233","article-title":"Molecular mechanism in \u03b1-glucosidase and glucoamylase","volume":"61","author":"Chiba","year":"1997","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1111\/liv.15716","article-title":"Investigating the role of lipid genes in liver disease using fatty liver models of alcohol and high fat in zebrafish (Danio rerio)","volume":"43","author":"Shihana","year":"2023","journal-title":"Liver Int."},{"key":"ref_47","first-page":"1069718","article-title":"Targeting peroxisome proliferator-activated receptors using thiazolidinediones: Strategy for design of novel antidiabetic drugs","volume":"2017","author":"Thangavel","year":"2017","journal-title":"Int. J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Dixon, E.D., Nardo, A.D., Claudel, T., and Trauner, M. (2021). The role of lipid sensing nuclear receptors (PPARs and LXR) and metabolic lipases in obesity, diabetes and NAFLD. Genes, 12.","DOI":"10.3390\/genes12050645"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tahri-Joutey, M., Andreoletti, P., Surapureddi, S., Nasser, B., Cherkaoui-Malki, M., and Latruffe, N. (2021). Mechanisms mediating the regulation of peroxisomal fatty acid beta-oxidation by PPAR\u03b1. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168969"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.biochi.2016.12.019","article-title":"The role and regulation of the peroxisome proliferator activated receptor alpha in human liver","volume":"136","author":"Kersten","year":"2017","journal-title":"Biochimie"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Duszka, K., Gregor, A., Guillou, H., K\u00f6nig, J., and Wahli, W. (2020). Peroxisome proliferator-activated receptors and caloric restriction\u2014Common pathways affecting metabolism, health, and longevity. Cells, 9.","DOI":"10.3390\/cells9071708"},{"key":"ref_52","first-page":"704","article-title":"CRISPR\/Cas9-mediated knockout of Abcd1 and Abcd2 genes in BV-2 cells: Novel microglial models for X-linked Adrenoleukodystrophy","volume":"1864","author":"Raas","year":"2019","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.2174\/1389557520666200619121003","article-title":"Structure-activity relationships of natural and synthetic indole-derived scaffolds as \u03b1-glucosidase inhibitors: A mini-review","volume":"20","author":"Wang","year":"2020","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sharchil, C., Vijay, A., Ramachandran, V., Bhagavatheeswaran, S., Devarajan, R., Koul, B., Yadav, D., and Balakrishnan, A. (2022). Zebrafish: A model to study and understand the diabetic nephropathy and other microvascular complications of type 2 diabetes mellitus. Vet. Sci., 9.","DOI":"10.3390\/vetsci9070312"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1152\/physrev.00038.2016","article-title":"Little fish, big data: Zebrafish as a model for cardiovascular and metabolic disease","volume":"97","author":"Gut","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nrg2091","article-title":"Animal models of human disease: Zebrafish swim into view","volume":"8","author":"Lieschke","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s11094-006-0115-6","article-title":"Synthesis and antimicrobial activity of 2, 4-dioxothiazolidine-5-acetic acid amides","volume":"40","author":"Zimenkovskii","year":"2006","journal-title":"Pharm. Chem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s00044-016-1508-z","article-title":"Synthesis and in vitro cancer cell growth inhibition evaluation of 11-amino-modified 5-Me-indolo[2,3-b]quinolines and their COMPARE analyses","volume":"25","author":"Okada","year":"2016","journal-title":"Med. Chem. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Sheir, S.K., Elmongy, E.I., Mohamad, A.H., Osman, G.Y., Bendary, S.E., Ahmed, A.A., Binsuwaidan, R., and El-Sayed, I.E. (2023). Molluscicidal and Larvicidal Potency of N-Heterocylic Analogs against Biomophalaria alexandrina Snails and Schistosoma mansoni Larval Stages. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15041200"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"21835","DOI":"10.1007\/s11356-020-11857-y","article-title":"Ameliorative effects of 9-diaminoacridine derivative against Ehrlich ascites carcinoma\u2013induced hepatorenal injury in mice","volume":"28","author":"Tousson","year":"2021","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/ptr.2794","article-title":"Anti-inflammatory properties of cryptolepine","volume":"23","author":"Olajide","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"459723","DOI":"10.1155\/2013\/459723","article-title":"Inhibition of neuroinflammation in LPS-activated microglia by cryptolepine","volume":"2013","author":"Olajide","year":"2013","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1517\/13543784.15.9.1039","article-title":"The potential of antidiabetic thiazolidinediones for anticancer therapy","volume":"15","author":"Galli","year":"2006","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"624","DOI":"10.2174\/1573406415666190515093657","article-title":"Novel Hybrids of pyrazolidinedione and benzothiazole as TZD analogues. rationale design, synthesis and in vivo anti-diabetic evaluation","volume":"15","author":"Haroun","year":"2019","journal-title":"Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ahmed, Y.M., Abdelgawad, M.A., Shalaby, K., Ghoneim, M.M., AboulMagd, A.M., Abdelwahab, N.S., Hassan, H.M., and Othman, A.M. (2022). Pioglitazone synthetic analogue ameliorates streptozotocin-induced diabetes mellitus through modulation of ACE 2\/angiotensin 1\u20137 via PI3K\/AKT\/mTOR signaling pathway. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030341"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Galal-Khallaf, A., Al-Awthan, Y.S., Al-Duais, M.A., and Mohammed-Geba, K. (2022). Nile crab Potamonautes niloticus shell extract: Chromatographic and molecular elucidation of potent antioxidant and anti-inflammatory capabilities. Bioorg. Chem., 127.","DOI":"10.1016\/j.bioorg.2022.106023"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"485","DOI":"10.2337\/db11-0588","article-title":"Heritable transmission of diabetic metabolic memory in zebrafish correlates with DNA hypomethylation and aberrant gene expression","volume":"61","author":"Olsen","year":"2012","journal-title":"Diabetes"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1177\/1932296818805074","article-title":"Insulin units and conversion factors: A story of truth, boots, and faster half-truths","volume":"13","author":"Knopp","year":"2019","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Butt, S.S., Badshah, Y., Shabbir, M., and Rafiq, M. (2020). Molecular docking using chimera and autodock vina software for nonbioinformaticians. JMIR Bioinform. Biotechnol., 1.","DOI":"10.2196\/14232"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Badr, M., Elmongy, E.I., Elkhateeb, D., Moemen, Y.S., Khalil, A., Ali, H., Binsuwaidan, R., Awadallah, F., and El Sayed, I.E. (2024). In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine\/Sulfonamide Hybrids Targeting Topoisomerases I and II. Pharmaceuticals, 17.","DOI":"10.3390\/ph17111487"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/7\/1023\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:07:42Z","timestamp":1760033262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/7\/1023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":70,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ph18071023"],"URL":"https:\/\/doi.org\/10.3390\/ph18071023","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]}}}