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Background: Pyrazolopyrimidine heterocycle and its isosteres represent the main scaffold for many pharmacologically active drugs including anti-inflammatory agents. The COX-2 inhibitors are the principal gate for the design of new safe and potent anti-inflammatory agents. Methods: Novel derivatives of pyrazolo[1,5-a] pyrimidines were synthesized and screened in vivo and in vitro for their anti-inflammatory potential. Results: Within the constructed compounds, compound 11 was the most active compound on IL-6 and TNF-α (percentage inhibition = 80 and 89%, respectively). In addition, compound 12 displayed the most inhibitory effect towards COX-2 (IC50 = 1.11 µM), whereas compound 11 recorded the highest COX-2 selectivity (S.I = 8.97). The target derivatives 11–14 displayed good edema inhibitory potential (46–68%) and compound 11 was the most potent candidate (ED50 = 35 mg/kg). Additionally, the most potent sPLA2-V inhibitors were compounds 11 and 13 (IC50 = 1 and 1.7 µM respectively). Regarding activity towards 15-LOX, derivative 12 was the most active compound with IC50 = 5.6 µM revealing higher inhibitory activity than nor-dihydroguaiaretic acid (IC50 = 8.5 µM). To confirm the anti-inflammatory potential of the target derivatives, molecular modeling was performed inside COX-2 and 15-LOX active sites. Conclusion: Display discoveries increment the plausibility that these pyrazolo[1,5-a]pyrimidines might act as a beginning point for the improvement of anti-inflammatory agents.

Pyrazolo[3,4-d]pyrimidine had been attracted awesome interest due to its pharmacological potential especially as an anticancer. Several mechanisms of action were accounted for the anticancer potential of this privileged scaffold. Previous researches explained its role in binding with many receptors as cyclin-dependent kinases, epidermal growth factor receptor, Src kinase, m-TOR, and JAK kinase. Nevertheless, there is an incredible demand for the discovery of target-oriented compounds. In this review, we shed the light on the antitumor potential of this important fused heterocyclic system, different mechanisms of actions of this ring, and SAR studies towards many targets in a trial to pave the way for medicinal chemists to optimize this ring system in order to discover new anticancer agents with better selectivity and increased anticancer potential.

An effective method for synthesizing series of twenty-two new compounds 1, 2a,b, 3, 4a,b, 5a-e, 7, 8, 9, 10, 12, 13a-d, 15a,b was performed starting from reaction of 1,2,3-indenetrione thiourea, and ethyl cyanoacetate under microwave irradiation and / or 2-(1,3-dioxo-1H-inden-2(3H)-ylidene) hydrazine carbothioamide with acetic anhydride. Chemical structure of the obtained products has been established by spectroscopic techniques including FTIR, 1H NMR, 13C NMR, DEPT-135, and mass spectroscopy. The designed new compounds have been successfully examined in-vitro for their antifungal activities. The relation between the structure of the synthesized compounds and their activity against tomato damping-off disease caused by Fusarium oxysporum fungi was studied and favourable results were obtained. The antifungal studies indicated that compounds 1, 7, 4a and 5a-d exerted the highest antifungal activities, while 3 and 4b recorded the lowest effect. The obtained results confirmed the possibility of the application of ethyl 6′-amino-1,3-dioxo-2′-thioxo-1,2′,3,3′-tetrahydro-1′H-spiro[indene-2,4′-pyrimidine]-5′-carboxylate 1 as a new effective regulator of the vegetative growth of tomatoes. The molecular docking analysis was performed within succinate dehydrogenase (SDH) as a target enzyme in order to rationalize the promising findings obtained for the active compounds 1, 2a,b, 5a-d, 7, 8, 9, 10, 12, and 13a.

In search of unprecedented tri and/or tetrapod pharmacophoric conjugates, a series of 32 new 4-ethyl-1H-benzo[b][1,4]diazepin-2(3H)-ones were synthesized and properly elucidated using MS, IR, NMR, and elemental analysis. In vitro investigation of 11 compounds of this series, using a panel of two human tumor cell lines namely; human breast adenocarcinoma (MCF-7), and human colorectal carcinoma (HCT-116), revealed promising cytotoxic activities. Among all synthesized compounds, analogue 9 displayed maximum cytotoxicity with IC50 values of 16.19 ± 1.35 and 17.16 ± 1.54 μM against HCT-116 and MCF-7, respectively, compared to standard drug doxorubicin.

A series of 34 new pyrimido[2,1-c][1,2,4]triazine-3,4-diones were synthesized and fully characterized using IR, NMR, MS, and microanalytical analysis. In vitro investigation of 12 compounds of this series revealed promising antimicrobial activity of the conjugates 15a and 15f−j that were tagged with electron-withdrawing groups, with sensitivities ranging from 77% to as high as 100% of the positive control. The investigation of antimicrobial activity included Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6535, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 8739 (EC), and fungal strains Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404.