Design, synthesis, pharmacological evaluation, and in silico studies of the activity of novel spiro pyrrolo[3,4-d]pyrimidine derivatives.

In the present study, spiro compounds are shown to have distinctive characteristics because of their interesting conformations and their structural impacts on biological systems. A new family of functionalized spiro pyrrolo[3,4-d]pyrimidines is prepared via the one-pot condensation reaction of amino cyclohexane derivatives with benzaldehyde to prepare fused azaspiroundecanedione and azaspirodecenone/thione derivatives. A series of synthesized spiro compounds were scanned against DPPH and evaluated for their ability to inhibit COX-1 and COX-2. All compounds exhibit significant antiinflammatory activity, and they inhibited both COX-1 and COX-2 enzymes with a selectivity index higher than celecoxib as a reference drug. The most powerful and selective COX-2 inhibitor compounds were 11 and 6, with selectivity indices of 175 and 129.21 in comparison to 31.52 of the standard celecoxib. However, candidate 14 showed a very promising antiinflammatory activity with an IC50 of 6.00, while celecoxib had an IC50 of 14.50. Our findings are promising in the area of medicinal chemistry for further optimization of the newly designed and synthesized compounds regarding the discussed structure-activity relationship study (SAR), in order to obtain a superior antioxidant lead compound in the near future. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopic and elemental investigations.

Design, Synthesis, Molecular Docking, and Evaluation Antioxidant and Antimicrobial Activities for Novel 3-Phenylimidazolidin-4-One and 2-Aminothiazol-4-One Derivatives.

On our way to discovering and developing compounds that have an antioxidant impact compared to ascorbic acid and other biological activities, we designed, synthesized, and evaluated a new series of heterocyclic moieties drugs (1-11) as antioxidants and antimicrobial agents. As starting moieties, these new candidates were derived from two promising heterocyclic compounds, imidazoldin-4-one and thiazol-4-one. Firstly, diphenylimidazol 1 was obtained because of the cyclo condensation one-pot ternary reaction of urea, aniline, and chloroacetic acid under thermal conditions. Out of this starting compound, we could design and create new vital rings such as purine and triazine as in compounds 5 and 6, respectively. Secondly, the start thiazole derivative 7 was obtained from the intermolecular cyclization of thiourea, chloroacetic acid, p-nitobezaldehyde in the presence of sodium acetate. We synthesized various derivatives from this second starting compound 7 by being subjected to different reagents such as aniline, phenylenediamine, phenylhydrazine, and barbituric acid to yield 8, 9, 10, and 11, respectively. Using ascorbic acid as the standard compound, the pharmacological testing for antioxidant activity assessment of the produced derivatives was evaluated against ABTS (2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid). Candidate 6 exhibited the best activity as an antioxidant agent compared to ascorbic acid as a reference compound. Moreover, all compounds were evaluated as antimicrobial agents against a series of bacteria and fungi. Among all synthesized compounds, compound 6 achieved high efficiency against two types of fungi and four kinds of bacteria, as Clotrimazole and Ampicillin were used as the reference agents, respectively. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopical and elemental investigations.

Design, Synthesis, Biological Evaluation, 2D-QSAR Modeling, and Molecular Docking Studies of Novel 1H-3-Indolyl Derivatives as Significant Antioxidants.

Novel candidates of 3-(4-(thiophen-2-yl)-pyridin/pyran/pyrimidin/pyrazol-2-yl)-1H-indole derivatives (2-12) were designed by pairing the pyridine/pyrane/pyrimidine/pyrazole heterocycles with indole and thiophene to investigate their potential activities as (2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) inhibitors. The purpose of these derivatives' modification is to create high-efficiency antioxidants, especially against ABTS, as a result of the efficiency of this set of key heterocycles in the inhibition of ROS. Herein, 2D QSAR modeling was performed to recommend the most promising members for further in vitro investigations. Furthermore, the pharmacological assay for antioxidant activity evaluation of the yielded indole-based heterocycles was tested against ABTS (2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); by utilizing ascorbic acid as the standard. Candidate 10 showed higher antioxidant activity (IC50 = 28.23 µg/mL) than ascorbic acid itself which achieved (IC50 = 30.03 µg/mL). Moreover, molecular docking studies were performed for the newly designed and synthesized drug candidates to propose their mechanism of action as promising cytochrome c peroxidase inhibitors compared to ascorbic acid as a reference standard. Our findings could be promising in the medicinal chemistry scope for further optimization of the newly designed and synthesized compounds regarding the introduced structure-activity relationship study (SAR) in order to get a superior antioxidant lead compound in the near future.

Ecofriendly synthesis of pyrano[2,3-d]pyrimidine derivatives and related heterocycles with anti-inflammatory activities.

A versatile, efficient, clean, and facile method was used for the synthesis of pyrano[2,3-d]pyrimidine derivatives by the one-pot three-component condensation reaction of thiobarbituric acid and malononitrile with p-chlorobenzaldehyde, using Fe3 O4 or ZnO or Mn3 O4 as nanostructure catalysts. The catalyst could be easily recovered using an external magnet and reused for six cycles with almost a consistent activity. A series of polyheterocyclic compounds containing five and/or six rings fused with each other was designed. The anti-inflammatory activities for some of the newly synthesized compounds were evaluated. All the synthesized compounds were characterized on the basis of their elemental analyses and spectral data.