Rational Drug Discovery for Isoxazole Based VEGFR2 Inhibition.

Background: Inhibiting receptor-tyrosine-kinase (RTK) signalling pathways has emerged as a key focus of novel cancer therapy development. Vascular endothelial growth factor receptor (VEGFR) is a member of the RTK family and is required for vasculogenesis and angiogenesis. Because VEGFR 2 is the subtype responsible for cellular angiogenesis and vasculogenesis, blocking it will impair tumour cell blood supply, reducing their development, proliferation, and metastasis.

Molecular Docking, Pharmacokinetic and Molecular Simulation Analysis of Novel Mono-Carbonyl Curcumin Analogs as L858R/T790M/C797S Mutant EGFR Inhibitors.

Introduction: Curcumin, an anticancer natural compound with multiple pharmacological activities, has a weak pharmacokinetic and instability due to diketone moiety. Curcumin's stability challenges can be overcome by removing the diketone moiety and shortening the 7-carbon chain, resulting in mono-carbonyl analogs. Cancer proliferation is caused by the activation of Epidermal Growth Factor (EGFR) pathways.

A Review: Exploring Synthetic Schemes and Structure-activity Relationship (SAR) Studies of Mono-carbonyl Curcumin Analogues for Cytotoxicity Inhibitory Anticancer Activity.

Introduction: Cancer is the major cause of death globally. Cancer can be treated with naturally occurring Curcumin nuclei. Curcumin has a wide range of biological actions, including anti-inflammatory and anti-cancer properties.

Explorations of novel pyridine-pyrimidine hybrid phosphonate derivatives as aurora kinase inhibitors.

For developing novel therapeutic agents with good anticancer activities, a series of novel pyridine-pyrimidine hybrid phosphonate derivatives4(a-q) were synthesized by the Kabachnik-Fields method using CAN as catalyst. The compound 4o exhibited the most potent anticancer activity with an IC value of 13.62 μM, 17.

One pot synthesis, in silico study and evaluation of some novel flavonoids as potent topoisomerase II inhibitors.

A library of novel flavonoid derivatives with diverse heterocyclic groups was designed and efficiently synthesized. Structures of the newly synthesized compounds 4a-i and 8a-l have been characterized by H NMR, C NMR, MS and elemental analysis. Anticancer activities were evaluated against MCF-7, A549, HepG2 and MCF-10A by MTT based assay.

Synthesis and pharmacological screening of some novel anti-hypertensive agents possessing 5-Benzylidene-2-(phenylimino)-thiazolidin-4-one ring.

In the present study, fourteen derivatives comprising of 5-benzylidene-2-(phenylimino)-thiazolidin-4-one moiety were synthesized. The structures of synthesized compounds were established by elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data and tested for electrocardiographic, antiarrhythmic and antihypertensive activities. Compound 11 was found to be most potent in this series.

Pharmacophore optimization and design of competitive inhibitors of thymidine monophosphate kinase through molecular modeling studies.

A series of N(1) -(4-substituted-benzyl)-pyrimidines were subjected to 2D and 3D quantitative structure-activity relationship analyses. Statistically significant models were generated, and the most robust model for 2D quantitative structure-activity relationship was obtained using simulated annealing-multiple linear regression. The physicochemical descriptors, viz.

Synthesis and pharmacological evaluation of novel 1-(2-(benzoyl-substituted-2-phenyl-1H-indol-5-carbony) hydrazinyloxy) vinyl nitrate derivatives as potent non-ulcerogenic, analgesic and anti-inflammatory agents.

Six derivatives of 1-(2-(benzoyl-(substituted)-2-phenyl-1H-indole-5-carbony) hydrazinyloxy) vinyl nitrate were synthesized and tested in vivo for anti-inflammatory, analgesic, and ulcerogenic properties. Synthesized compounds shown significant anti-inflammatory activity comparable to that of Diclofenac sodium in the carrageenan-induced rat paw edema test and all of the compounds were found to be equipotent to Diclofenac sodium in the acetic acid induced writhing analgesic model. Out of six derivatives two derivatives found to produce no ulceration in stomach specimen of rats; nitric oxide seems to contribute to their excellent safety profile which supports several endogenous GIT defense mechanisms, including increase in mucus, bicarbonate secretions, increase in mucosal blood flow, and inhibition of the activation of pro-inflammatory cells by which NO-Indomethacin protects GI mucosa.

Design, synthesis, and evaluation of anti-inflammatory, analgesic, ulcerogenicity, and nitric oxide releasing studies of novel indomethacin analogs as non-ulcerogenic derivatives.

Most non-steroidal anti-inflammatory drugs (NSAIDs) suffer from the deadlier gastrointestinal (GI) toxicities. The free -COOH group is responsible for the GI toxicity associated with all traditional NSAIDs. In the present research work, the main objective was to develop new chemical entities as potential anti-inflammatory agents with no GI toxicities.

Design, synthesis and pharmacological screening of novel nitric oxide donors containing 1,5-diarylpyrazolin-3-one as nontoxic NSAIDs.

Various substituted 1,5-diarylpyrazol-3-one derivatives were synthesized and screened for analgesic, anti-inflammatory activities, ulcerogenic potential and for their ability to release nitric oxide. Most compounds exhibited significant analgesic and anti-inflammatory activities. It was interesting to note that out of ten compounds, 7j (59.

Design, synthesis and pharmacological screening of novel antihypertensive agents using hybrid approach.

Eight derivatives of general formula 2-(2-(4-(3-((5-substituted methylene)-4-oxo-2-(phenylimino)thiazolidin-3-yl)-2-hydroxypropylamino)benzoyl)hydrazinyl)-2-oxoethyl nitrate were synthesized and tested for electrocardiographic, antiarrhythmic, vasorelaxing and antihypertensive activity as well as for in-vitro nitric oxide (NO) releasing ability. Compound 8b 2-(2-(4-(3-(5-benzyliden-4-oxo-2-(phenylimino)thiazolidin-3-yl)-2-hydroxypropylamino)benzoyl)hydrazinyl)-2-oxoethyl nitrate, was the most potent in this series. The pharmacological results suggested that the antiarrhythmic effects of these compounds were related to their adrenolytic properties which are believed to be due to the presence of the 5-(substituted)methylen-2-(phenylimino)thiazolidin-4-one moiety with less bulky, electron donating substituent on the phenyl ring at 5th position of the thiazolidin-4-one.

Design, synthesis and evaluation of antiinflammatory, analgesic and ulcerogenicity studies of novel S-substituted phenacyl-1,3,4-oxadiazole-2-thiol and Schiff bases of diclofenac acid as nonulcerogenic derivatives.

Diclofenac sodium is being used for its anti-inflammatory actions since 28 years, but as all the NSAIDs are suffering from the deadlier GI toxicities, diclofenac sodium is also not an exception to these toxicities. The free -COOH group is thought to be responsible for the GI toxicity associated with all traditional NSAIDs. In the present research work, the main motto was to develop new chemical entities as potential anti-inflammatory agents with no GI toxicities.