New 1
H
-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesised to act as epidermal growth factor receptor inhibitors (EGFRIs). The synthesised derivatives were assessed for their
in vitro
anti-proliferative activities against A549 and HCT-116 cancer cells. Compounds
8, 10, 12a,
and
12b
showed potent anti-proliferative activities. Compound
12b
was the most promising member with IC
50
values of 8.21 and 19.56 µM against A549 and HCT-116, respectively. Compounds
8, 10, 12a,
and
12b
were evaluated for their kinase inhibitory activities against wild EGFR (EGFR
WT
). Compound
12b
was the most potent member showing an IC
50
value of 0.016 µM. In addition, compound
12b
showed noticeable activity against mutant EGFR (EGFR
T790M
) (IC
50
= 0.236 µM). Flow cytometric analyses revealed that compound
12b
is a good apoptotic inducer and can arrest the cell cycle at S and G2/M phases. Furthermore, it produced an 8.8-fold increase in BAX/Bcl-2 ratio. Molecular docking studies were carried out against EGFR
WT
and EGFR
T790M
.
Three novel series of 1,2,4-triazole derivatives were designed and synthesized as potential adenosine A2B receptor antagonists. The design of the new compounds depended on a virtual screening of a previously constructed library of compounds targeting the human adenosine A2B protein. Spectroscopic techniques including 1 H nuclear magnetic resonance (NMR) and 13 C NMR, and infrared and mass spectroscopy were used to confirm the structures of the synthesized compounds. The in vitro cytotoxicity evaluation was carried out against a human breast adenocarcinoma cell line (MDA-MB-231) using the MTT assay, and the obtained results were compared with doxorubicin as a reference anticancer agent. In addition, in silico studies to propose how the two most active compounds interact with the adenosine A2B receptor as a potential target were performed. Furthermore, a structure-activity relationship analysis was performed, and the pharmacokinetic profile to predict the oral bioavailability and other pharmacokinetic properties was also explained. Four of our designed derivatives showed promising cytotoxic effects against the selected cancer cell line. Compound 15 showed the highest activity with an IC 50 value of 3.48 µM. Also, compound 20 revealed an equipotent activity with the reference cytotoxic drug, with an IC 50 value of 5.95 µM. The observed IC 50 values were consistent with the obtained in silico docking scores. The newly designed compounds revealed promising pharmacokinetic profiles as compared with the reference marketed drug.
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