{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:45:06Z","timestamp":1760035506000,"version":"build-2065373602"},"reference-count":59,"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":"Council of Scientific &amp; Industrial Research (CSIR)","award":["02(0304)\/17\/EMR-II","5U54MD007585-33"],"award-info":[{"award-number":["02(0304)\/17\/EMR-II","5U54MD007585-33"]}]},{"name":"National Institute on Minority Health and Disparities","award":["02(0304)\/17\/EMR-II","5U54MD007585-33"],"award-info":[{"award-number":["02(0304)\/17\/EMR-II","5U54MD007585-33"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Natural products play a crucial role in cancer treatment due to their ability to selectively target cancer cells. Andrographolide, a major constituent of Andrographis paniculata, exhibits potential anticancer properties. Considering the pharmacological importance of nitrogen-based heteroaromatic scaffolds, particularly pyrazole motifs, this study aimed to integrate the pyrazole pharmacophore with the andrographolide scaffold to develop novel therapeutic candidates. Methods: Twenty novel 3,19-(N-phenyl-3-aryl-pyrazole) acetals of andrographolide and isoandrographolide were synthesized and characterized using UV-Vis, FT-IR, NMR, and HRMS. Initial anticancer screening was conducted by the National Cancer Institute (NCI), USA, against 60 human cancer cell lines. The most promising compound, 1f (R = 4-F), was selected for further biological evaluation in the MDA-MB-231 breast cancer cell line. Results: The MTT assay results demonstrated that compound 1f exhibited strong, dose-dependent anti-proliferative effects. The apoptosis analysis of 1f revealed a time-dependent increase in apoptotic cells, and cell cycle studies indicated S phase arrest in MDA-MB-231 cells. Antioxidant activity via the DPPH assay identified compounds 1b (R = 3-NO2) and 2b (R = 3-NO2) as the most effective radical scavengers. The most active compounds were also evaluated for drug-likeness using in silico Lipinski\u2019s rule assessments. Conclusions: The synthesized 3,19-(N-phenyl-3-aryl-pyrazole) acetals of andrographolide and isoandrographolide exhibited promising anticancer and antioxidant properties. Among them, compound 1f showed the most significant activity, supporting its potential as a lead candidate for further anticancer drug development.<\/jats:p>","DOI":"10.3390\/ph18071026","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T15:36:58Z","timestamp":1752161818000},"page":"1026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel 3,19-(N-Phenyl-3-(4-fluorophenyl)-pyrazole) Acetal of Andrographolide Promotes Cell Cycle Arrest and Apoptosis in MDA-MB-231 Breast Cancer Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Siva Kumar","family":"Rokkam","sequence":"first","affiliation":[{"name":"Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Puttaparthi 515134, Andhra Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahjalal","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Biology and Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yashwanth","family":"Inabathina","sequence":"additional","affiliation":[{"name":"Department of Biology and Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0838-6940","authenticated-orcid":false,"given":"Lakshminath","family":"Sripada","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Puttaparthi 515134, Andhra Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivas","family":"Nanduri","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research, Balanagar, Hyderabad 500037, Telangana, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0782-2539","authenticated-orcid":false,"given":"Balasubramanyam","family":"Karanam","sequence":"additional","affiliation":[{"name":"Department of Biology and Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nageswara Rao","family":"Golakoti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Puttaparthi 515134, Andhra Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Maj\u00e9rus, M.-A. 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