Current Discovery Progress of Some Emerging Anti-infective Chalcones: Highlights from 2016 to 2017.

The anti-infective potentials of the natural products are very well known for centuries and are a part of traditional healing. The foremost therapeutic classes include flavones, isoflavones, flavonols, flavanones, flavanols, proanthocyanidins, anthocyanidins, chalcones, and aurones. The chalcone or 1,3-diphenyl-2E-propene-1-one represents the class of natural products which are comprised of benzylideneacetophenone function; i.e. two aromatic moieties linked together by an α, ß-unsaturated carbonyl bridge comprising three-carbons. At present, chalcone is one of the privileged scaffolds that can be synthesized in the laboratory to derive different pharmacologically active compounds. This article is the continued form of the previously published work on anti-infective perspectives of chalcones (highlighted till 2015). The current work emphasizes on the discovery process of the chalcone in the period of 2016 to 2017 on malaria, trypanosomiasis, leishmaniasis, filaria, tuberculosis, netamodes, Human Immunodeficiency Virus (HIV), Tobacco Mosaic Virus (TMV), Severe Acute Respiratory Syndrome (SARS), and miscellaneous conditions. This review comprehensively focuses on the latest progress related with the anti-infective chalcones. The content includes the crucial structural features of chalcone scaffold including structure-activity relationship(s) along with their plausible mechanism of action(s) from the duration Jan 2016 to Dec 2017. This literature will be of prime interest to medicinal chemists in getting ideas and concepts for better rational development of potential anti-infective inhibitors.

Triggering PIK3CA Mutations in PI3K/Akt/mTOR Axis: Exploration of Newer Inhibitors and Rational Preventive Strategies.

BACKGROUND: PIK3CA gene was found in generation of p110 alpha (p110α) protein through an instruction process. p110 alpha acts as a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) proceed phosphorylation of signal molecules through PI3K pathway. This PI3K involved in regulation of cellular growth, transformation, adhesion, apoptosis, survival and motility. In some situations the PI3K/Akt pathway get altered due to mutation in PIK3CA gene produced oncogenic event in human malignancy. METHODS: The goal of this work is to describe the PI3K signaling pathway including mutational activation of PIK3CA gene and inhibitors have been developed or under clinical trials for the targeting of PI3K or PI3KR kinases. RESULTS: Various inhibitors such as Morpholine, pyrimidines, benzenesulfonamide, pyridopyrimidinone, imidazo[1,5]naphthyridine, benzeneacylhydrazones, thienopyrimidine, aminopyridopyrimidine, imidazopyridine, imidazo[1,2-a]pyridine, thiazolopyrimidinone, quinolines and quinoxalines, thieno[3,2-b]pyran-7-one, morpholino-1,3-benzoxazines, quinalozinones, pyrido [3,2-d]pyrimidines, benzo[d]thiazol-2-yl)acetamide, aminopyrimidines, chalcone , azaindole, pyrazolopyrimidine and pyridine, thienobenzoxepin, phenylquinazolines , pyrazolo[1,5-a]pyridines , imidazolo-pyrimidine etc. were investigated under laboratory level as PI3K inhibitors in which few having PI3K and mTOR dual inhibitory activities. CONCLUSION: After a long term of prognostic standpoint, PIK3CA mutations discussed as a major target for various cancers. These PIK3CA mutations were found in various exon including 1,2,4,6,7,9,13,18 and 20 which may be a cause of different cancers such as breast, colon, ovarian, gastric, brain, lung etc. In clinical trials these mutations still remain question marks for presence or absence to the scientist regarding future perspective. The opinion of these studies is to development of more specific inhibitors of PI3K pathway which produce tremendous impact on various cancers developed due to PIK3CA mutations.

Mutant B-Raf Kinase Inhibitors as Anticancer Agents.

The Ras/Raf/MEK/ERK signaling pathway involves various kinases in which each kinase is associated with one another through signals and regulates cell proliferation, differentiation and apoptosis. This pathway is dysregulated almost in all cancers due to the amplification and genetic mutation of various components of the pathway. The genetic mutations have been reported to cause drug resistance to the current chemotherapy of melanomas. B-Raf is one of the most commonly mutated proto-oncogenes and plays a significant role in the development of numerous cancers of high clinical impact. Therefore, mutant B-Raf kinase may be a promising therapeutic target for the development of novel anticancer drugs. Many BRAF inhibitors discovered during the last decade showed promising anticancer activity, especially on tumors that harbor BRAFV600E mutations. Currently, vemurafenib and dabrafenib are USFDA approved drugs used as B-Raf inhibitors. Few drugs which are under clinical development phases such as LGX818, GDC0879, XL281, ARQ736, PLX3603 (RO5212054), and RAF265 etc. pave the path for further designing of B-Raf inhibitors. The present review focuses primarily on the Ras/Raf/MEK/ERK signaling pathway with mutant B-Raf as a therapeutic target for anticancer drug development. The essential pharmacophoric features of B-Raf inhibitors, their structure activity relationships (SARs) and molecules under clinical trials have been highlighted.

Thiazolidine-2,4-diones as multi-targeted scaffold in medicinal chemistry: Potential anticancer agents.

A variety of substituents on the thiazolidine-2,4-dione(TZD) nucleus have provided a wide spectrum of biological activities by the using of different mechanism on various target sites. PPARγ ligands have recently been demonstrated to affect cell proliferation, differentiation and apoptosis of different cell types. Currently, some of the TZDs are designed for the treatment of human cancers expressing high levels of PPARγ because it is assumed that activation of PPARγ mediates their anticancer activity. Another site for TZDs is survival signaling pathways under growth factor loops have been implicated in cancer development, progression, and metastasis. The Raf/MEK/ERK, Wnt and PI3K/Akt signalling cascades are the most commonly up-regulated in human cancers. In the present review, various derivatives of thiazolidine-2,4-diones its SAR and different signaling pathways involved to produce anticancer activity been highlighted.