TY  - JOUR
A1  - Othman, Eman M.
A1  - Bekhit, Amany A.
A1  - Anany, Mohamed A.
A1  - Dandekar, Thomas
A1  - Ragab, Hanan M.
A1  - Wahid, Ahmed
T1  - Design, Synthesis, and Anticancer Screening for Repurposed Pyrazolo[3,4-d]pyrimidine Derivatives on Four Mammalian Cancer Cell Lines
JF  - Molecules
N2  - The present study reports the synthesis of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines. Results revealed that two (5 and 7) of the three synthesized compounds (5, 6, and 7) showed high cytotoxic activity against all tested cell lines with IC50 values in the micro molar concentration. Our in vitro results show that there is no significant apoptotic effect for the treatment with the experimental compounds on the viability of cells against A549 cells. Ki67 expression was found to decrease significantly following the treatment of cells with the most promising candidate: drug 7. The overall results indicate that these pyrazolopyrimidine derivatives possess anticancer activity at varying doses. The suggested mechanism of action involves the inhibition of the proliferation of cancer cells.
KW  - pyrazolo[3,4-d]pyrimidine
KW  - anticancer activity
KW  - apoptosis
KW  - Ki67
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239734
SN  - 1420-3049
VL  - 26
IS  - 10
ER  - 
TY  - JOUR
A1  - El-Hawary, Seham S.
A1  - Sayed, Ahmed M.
A1  - Mohammed, Rabab
A1  - Hassan, Hossam M.
A1  - Rateb, Mostafa E.
A1  - Amin, Elham
A1  - Mohammed, Tarek A.
A1  - El-Mesery, Mohamed
A1  - Bin Muhsinah, Abdullatif
A1  - Alsayari, Abdulrhman
A1  - Wajant, Harald
A1  - Anany, Mohamed A.
A1  - Abdelmohsen, Usama Ramadan
T1  - Bioactive brominated oxindole alkaloids from the Red Sea sponge Callyspongia siphonella
JF  - Marine Drugs
N2  - In the present study, LC-HRESIMS-assisted dereplication along with bioactivity-guided isolation led to targeting two brominated oxindole alkaloids (compounds 1 and 2) which probably play a key role in the previously reported antibacterial, antibiofilm, and cytotoxicity of Callyspongia siphonella crude extracts. Both metabolites showed potent antibacterial activity against Gram-positive bacteria, Staphylococcus aureus (minimum inhibitory concentration (MIC) = 8 and 4 µg/mL) and Bacillus subtilis (MIC = 16 and 4 µg/mL), respectively. Furthermore, they displayed moderate biofilm inhibitory activity in Pseudomonas aeruginosa (49.32% and 41.76% inhibition, respectively), and moderate in vitro antitrypanosomal activity (13.47 and 10.27 µM, respectively). In addition, they revealed a strong cytotoxic effect toward different human cancer cell lines, supposedly through induction of necrosis. This study sheds light on the possible role of these metabolites (compounds 1 and 2) in keeping fouling organisms away from the sponge outer surface, and the possible applications of these defensive molecules in the development of new anti-infective agents.
KW  - Callyspongia siphonella
KW  - LC-HRESIMS
KW  - metabolomic profiling
KW  - oxindole alkaloids
KW  - tisindoline
KW  - antibacterial
KW  - antibiofilm
KW  - antitrypanosomal
KW  - anticancer
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201485
VL  - 17
IS  - 8
ER  -