Synthesis, Molecular Docking and Dynamics Simulation Studies of New 7-oxycoumarin Derivatives as Potential Antioxidant Agents.

METHOD: Two new series of 4-styryl-7-oxycoumarin derivatives 3a-i and 4-styryl-7- oxycoumarinyl Mannich bases 6a-r were designed and synthesized. Ten compounds were evaluated for their antioxidant activity in vitro against DPPH and in vivo against lipid Peroxidation, Superoxide Dismutase (SOD), Glutathione-s-Transferase (GST) and Catalase (CAT) activities. Molecular modeling study was performed to predict the mode of binding of the target compounds in the binding site. RESULTS & CONCLUSION: Although the tested compounds showed moderate to low dose dependent DPPH inhibition activities in vitro, most of them displayed remarkable antioxidant effects in vivo. Compounds 1, 6b, 3c and 6r displayed significant decrease in MDA, SOD and CAT enzyme levels in H2O2 treated rats. Free binding energy was estimated by docking, MM-PBSA and MM-GBSA. Molecular dynamics simulation followed by MM-GBSA calculation was correlated to the antioxidant effect. Compound 1 illustrated the highest MM-GBSA value (-20.38) and the best antioxidant effect.

Triazolopyrimidines and Thiazolopyrimidines: Synthesis, Anti-HSV-1, Cytotoxicity and Mechanism of Action.

BACKGROUND: Several commercial drugs utilized in the treatment of HSV containing pyrimidine moiety. Because of the ineffectiveness of virus drugs due to the resistance of the patient's immune system, there is a pressing need to prepare new compounds that are effective in the treatment of various viruses. RESULTS: Merged pyrimidine derivatives were designed by one pot synthesis of pyrimidinethione derivative with halogenated compounds. The structure of all prepared compounds was characterized by their spectroscopic data and also, their ability to inhibit the in vitro replication of HSV-1 was estimated. Amongst the tested compounds 2-acetyl-3-methyl-5-(p-tolyl)indeno[1,2-d]thiazolo[3,2- a]pyrimidin-6(5H)-one (9b) and ethyl 3-methyl-6-oxo-5-(p-tolyl)-5,6-dihydroindeno[1,2-d]thiazolo- [3,2-a]pyrimidine-2-carboxylate (9c), caused viral inhibition over 90%. Furthermore, the selectivity indices of the tested compounds are high and have weak cytotoxicity (all samples were checked, not chosen on cytotoxicity basis, we only utilize secure concentrations of every compound). CONCLUSION: We succeeded in this context to synthesize a new series of potent fused pyrimidine derivatives as anti-HSV-1.

Anti-HSV-1 activity and mechanism of action of some new synthesized substituted pyrimidine, thiopyrimidine and thiazolopyrimidine derivatives.

A series of heterocyclic derivatives 2-16 conjugated with tetrahydronaphthalene moiety were synthesized as antiviral agents by using 1-(5,6,7,8-tetrahydronaphthalen-2-yl)ethanone as starting material. The antiviral screening showed that many of these obtained compounds have good antiviral activities comparable to Acyclovir as reference control. Two compounds 13 and 15 gave over 90% inhibition and considered to be highly promising and on confirming their activity and comparing them to antiviral activity of Acyclovir. The detailed synthesis, spectroscopic data, and antiviral screening for synthesized compounds were reported.

Anticancer activities of some newly synthesized pyridine, pyrane, and pyrimidine derivatives.

A series of pyridine, pyrane, and pyrimidine derivatives (2-11) were newly synthesized using nitrobenzosuberone 1 as a starting material. The antitumor activities of the synthesized compounds were evaluated utilizing 59 different human tumor cell lines, representing leukemia, melanoma, lung, colon, brain, ovary, breast, prostate as well as kidney. Some of the tested compounds especially 2, 3, 4c, 6, 7, 9b, 10a, and 11 exhibited better in vitro antitumor activities at low concentration (log(10) GI(50) = -4.7) against the used human tumor cell lines. Additionally, compounds 3, 4c, 6, 7, and 9b were highly selective to inhibit leukemia cell lines. The detailed synthesis, spectroscopic data and antitumor properties for the synthesized compounds were reported.