Advances in structural identification of some thieno[2,3-d]pyrimidine scaffolds as antitumor molecules: Synthetic approaches and control programmed cancer cell death potential.

Thieno[2,3-d]pyrimidine fragment is not only bioistostere to quinazoline ring but also to purines which exist in nucleic acids responsible for several key biological processes of the living cells, thus it is of a great interest for many researchers. Thieno[2,3-d]pyrimidine ring has become an important scaffold for different compounds with versatile pharmacological activities including anticancer. These compounds exert their anticancer activity through variant mechanisms of action; one of these is the induction of different programmed cell death types as apoptosis and necroptosis which is an effective approach for cancer treatment.

Design, synthesis, antineoplastic activity of new pyrazolo[3,4-d]pyrimidine derivatives as dual CDK2/GSK3β kinase inhibitors; molecular docking study, and ADME prediction.

In the current study, novel pyrazolo[3,4-d]pyrimidine derivatives 5a-h were designed and synthesized as targeted anti-cancer agents through dual CDK2/GSK-3β inhibition. The designed compounds demonstrated moderate to potent activity on the evaluated cancer cell lines (MCF-7 and T-47D). Compounds 5c and 5 g showed the most promising cytotoxic activity against the tested cell lines surpassing that of the used reference standard; staurosporine.

Design, synthesis, anticancer evaluation, and in silico studies of some thieno[2,3-d]pyrimidine derivatives as EGFR inhibitors.

New series of 20 thieno[2,3-d]pyrimidine derivatives have been synthesized. The National Cancer Institute evaluated all the newly synthesized compounds for their antiproliferative activity against a panel of 60 cancer cell lines. Compound 7b exhibited a remarkable antineoplastic activity at 10 µM dose and was therefore tested at five dose concentrations.

Novel pyrazole-based COX-2 inhibitors as potential anticancer agents: Design, synthesis, cytotoxic effect against resistant cancer cells, cell cycle arrest, apoptosis induction and dual EGFR/Topo-1 inhibition.

Novel differently substituted pyrazole derivatives were designed, synthesized and evaluated for their anticancer activity. All compounds selectively inhibited COX-2 enzyme (IC = 0.043-0.

Synthesis and biological evaluation of halogenated phenoxychalcones and their corresponding pyrazolines as cytotoxic agents in human breast cancer.

Novel halogenated phenoxychalcones and their corresponding -acetylpyrazolines were synthesised and evaluated for their anticancer activities against breast cancer cell line (MCF-7) and normal breast cell line (MCF-10a), compared with staurosporine. All compounds showed moderate to good cytotoxic activity when compared to control. Compound was the most active, with IC = 1.

Design and Synthesis of Novel Ibuprofen Derivatives as Selective COX-2 Inhibitors and Potential Anti-Inflammatory Agents: Evaluation of PGE2, TNF-α, IL-6 and Histopathological Study.

Background: The reported binding mode of ibuprofen in the COX-2 binding site indicated that the carboxylic group binds with Arg-120 and Tyr-355 at the entrance of the cyclooxygenase channel and does not extend into the pocket. This accounted for the non-selectivity of ibuprofen. Based on this fact, we assumed that extending the length of the carboxylic acid moiety in ibuprofen and adding more bulky rigid groups as well as bulky groups carrying H-bonding functions might increase the selectivity and reduce the side effects of ibuprofen while maintaining its analgesic and anti-inflammatory activities.

Novel tetrazole-based selective COX-2 inhibitors: Design, synthesis, anti-inflammatory activity, evaluation of PGE, TNF-α, IL-6 and histopathological study.

To search for effective and selective COX-2 inhibitors, four novel series of tetrazole derivatives were designed based on bioisosteric replacement of SONH in celecoxib with tetrazole ring incorporating different central moieties as chalcone (2a-f), isoxazole (3a-c) or pyrazole (4a-c & 5a-c). Target tetrazoles were synthesized and their structures were confirmed by spectroscopic techniques and elemental analyses. All target compounds were more selective for COX-2 isozyme than COX-1 when compared to standard drugs indomethacin and celecoxib.

Uses of cyclohexane-1,3-dione for the synthesis of 1,2,4-triazine derivatives as anti-proliferative agents and tyrosine kinases inhibitors.

Tetrahydrobenzo[b]thiophene derivatives were well known to be biologically active compounds and many of them occupy a wide range as anticancer agent drugs. One of our main aim of this work was to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. To achieve this goal, our strategy was to synthesize a series of novel 1,2,4-triazines as efficient anticancer drugs with low cytotoxicity and good bioavailability properties using cyclohexane-1,3-dione and 3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-2-diazonium chloride to give the 2-(2-(2,6-dioxocyclohexylidene)hydrazinyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (3) as the key starting material for many heterocyclization reactions.

Synthesis, and anti-proliferative, Pim-1 kinase inhibitors and molecular docking of thiophenes derived from estrone.

Heterocyclization of steroids were reported to give biologically active products where ring D modification occured. Estrone (1) was used as a template to develop new heterocyclic compounds. Ring D modification of 1 through its reaction with cyanoacetylhydrazine and elemental sulfur gave the thiophene derivative 3.