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• A variety of tri-substituted pyrazole derivatives 3 - 15 were synthesized and evaluated for their anti-inflammatory, analgesic, antipyretic and ulcerogenic properties. • Some of the tested conjugates showed promising biological observations comparable to standard reference celecoxib, in addition, to their safety margin for gastric mucosa when evaluated for their ulcer-producing activity. • The most potent derivatives 3a, 3b, 6, 8 and 11 were assayed for their COX-2, TNF-α, PGE2 and IL1β levels in rat paws using the carrageenan inflammation model with the ELISA kit. • Compound 8 possesses the best promising anti-inflammatory observations, antipyretic effect and long-lasting analgesic activity without ulcerogenic potential in addition to showing mutual inhibitory effects on all tested enzymes. • A molecular docking study was introduced to recognize the binding interactions of the most potent candidates into active sites of COX-2 and TNF-α. • Compound 8 has the best binding interaction scores with both targeted enzymes that supported its obtained bio-observations and proves that it has the potential to be developed into an anti-inflammatory drug. Starting from the precursors 3-(4-methoxyphenyl)-1H-pyrazole-4-carbaldehyde (1) and 3-(4-bromophenyl)-1-ethyl-1 H -pyrazole-4-carbaldehyde (2), a variety of trisubstituted pyrazole derivatives 3 - 15 were synthesized and evaluated for their anti-inflammatory, analgesic, antipyretic and ulcerogenic properties. Derivatives 3a, 3b, 6, 8 and 11 showed promising anti-inflammatory observations with potencies of 99.5, 100.3, 92.4, 77.1 and 103.1, respectively, compared with celecoxib the used standard reference, they also exhibited a promising onset action of analgesic with efficiency superior to the used reference drug, in addition to their antipyretic effect and safety margin for gastric mucosa compared with the reference drugs. Based on the obtained observations, derivatives 3a, 3b, 6, 8 and 11 were assayed for their COX-2, TNF- α , PGE2 and IL1 β levels in rat paws using the carrageenan inflammation model with the ELISA kit. Compound 8 has the best promising anti-inflammatory observations, antipyretic effect and long-lasting analgesic activity without ulcerogenic potential in addition to showing mutual inhibitory effects on all tested enzymes. Furthermore, a molecular docking study was introduced to recognize the binding interactions of the most potent candidates 3a, 3b, 6, 8 and 11 into the active sites of COX-2 and TNF- α. Compound 8 has the best binding interaction scores with both targeted enzymes that supported its obtained bio-observations and prove that it has the potential to be developed into an anti-inflammatory drug. [Display omitted] [ABSTRACT FROM AUTHOR]

• Isolation and characterization of eight bioactive compounds from brown alga sargassum platycarpum for the first time. • Evaluation of the in vitro anticancer activity against HepG-2 cell line. • Computations of MEP, EHOMO, ELUMO and global properties by DFT methods. • Molecular docking study. • Bioactivity Score, drug-likeness and ADMET studies. Image, graphical abstract Recently, macroalgae or seaweeds serve as a treasure of potential drugs for cancer therapy. The present study investigated the cytotoxic activity of eight compounds isolated from the brown alga Sargassum platycarpum for the first time. These isolates were identified as hexadecanoic acid (1), oleic acid (2), saringosterol (3 and 4 , 1:1 mixture of C-24epimers), β -sitosterol (5), glycoglycerolipid (6), loliolide (7) and Kjellmanianone (8) by spectroscopic techniques. Two epimers of saringosterol, (24- R)-saringosterol (3) and (24- S)-saringosterol (4), were subsequently separated by HPLC. (24- S)-saringosterol (4) and (24- R)-saringosterol (3) exhibited potent cytotoxicity against HepG-2 cells with IC 50 of 0.10±0.00 and 0.11±0.00 µM, respectively with compared to standard 5-Fluorouracil (IC 50 of 0.63±0.28 µM) and other isolates. MEP, E HOMO , E LUMO and global properties of all isolated compounds are computed by DFT methods. Molecular docking study showed that most of the isolated compounds especially compounds 3 and 4 interact strongly with 4PYP with the highest binding energies maintained that the high cytotoxic activity of these compounds against HepG-2 cells in the experimental part. Bioactivity Score, Drug-Likeness and ADMET studies supported the potential biological activities of most isolated compounds especially compounds 3 and 4 and also created attention for developing them to act as good candidates. [ABSTRACT FROM AUTHOR]