Abstract
Cancer weakens the immune system which fails to fight against the rapidly growing cells. Among the various types of cancers, prostate cancer (PCa) is causing greater number of deaths in men after lung cancer, demanding advancement to prevent, detect and treat PCa. Several small molecule heterocycles and few peptides are being used as oncological drugs targeting PCa. Heterocycles are playing crucial role in the development of novel cancer chemotherapeutics as well as immunotherapeutics. Indole skeleton, being a privileged structure has been extensively used for the discovery of novel anticancer agents and the application of indole derivatives against breast cancer is well documented. The present article highlights the usefulness of indole linked heterocyclic compounds as well as the fused indole derivatives against prostate cancer.
A mild heteroatom methylation protocol using trimethyl phosphate (TMP)-Ca(OH)2 combination has been developed, which proceeds in DMF, or water, or under neat conditions at 80 oC or at room temperature. A series of O-, N- and S-nucleophiles, including phenols, sulfonamides, N-heterocycles such as 9H-carbazole, indole derivatives, 1,8-naphthalimide, and aryl/alkyl thiols are suitable substrates of this protocol. The high efficiency, operational simplicity, scalability, cost-efficiency, and environmental friendly nature of this protocol make it an attractive alternative to the conventional base prompted heteroatom methylation procedures.
Optically active indole derivatives are ubiquitous in natural products and widely recognized as privileged components in pharmacologically relevant compounds. Therefore, developing catalytic asymmetric approaches for constructing indole derivatives is highly desirable. In this short review, transition-metal-catalyzed enantioselective synthesis of indoles from 2-alkynylanilines is summarized.
1 Introduction
2 Aminometalation triggered asymmetric cross-coupling reaction/insertion
2.1 Asymmetric Cross-Coupling Reaction
2.2 Asymmetric insertion of C=O, C=C and C≡N bonds
3 Asymmetric relay catalysis
4 Conclusion
The present work demonstrates γ-aminocyclopentenones as suitable surrogate for reactive cyclopentadienone via pseudocine-substitution manifold which enables its orchestrated annulation with tailored bis-nucleophiles and furnish complex β,γ-annulated cyclopentanoids or indole-based polycyclic...
Herein we report crystallographic comparison of some geometrical and structural features for a series of biologically relevant bis-indole derivatives. Selected bond distances and bond angles of interest in a series of bis-indole derivatives have been discussed in detail. The biological activity of the substances has been correlated with based the structure-activity relationships (SAR) base which provides the different possibility of activity (Pa) and possibility of inactivity (Pi). For a better understanding of the packing interactions existing among these derivatives, an overview of crystal structure analysis with emphasis on the intramolecular hydrogen bonding in some bis-indole derivatives is presented. The role of hydrogen bonding in the crystal structure assembly of bis-indole derivatives has been found to be predominant and this observation reveals significant impact of hydrogen bonding in high value of drug-likeness of these bio-molecules.
Crosstalk between the gut microbiome and the host plays an important role in animal development and health. Small compounds are key mediators in this host–gut microbiome dialogue. For instance, tryptophan metabolites, generated by biotransformation of tryptophan through complex host–microbiome co-metabolism can trigger immune, metabolic, and neuronal effects at local and distant sites. However, the origin of tryptophan metabolites and the underlying tryptophan metabolic pathway(s) are not well characterized in the current literature. A large number of the microbial contributors of tryptophan metabolism remain unknown, and there is a growing interest in predicting tryptophan metabolites for a given microbiome. Here, we introduce TrpNet, a comprehensive database and analytics platform dedicated to tryptophan metabolism within the context of host (human and mouse) and gut microbiome interactions. TrpNet contains data on tryptophan metabolism involving 130 reactions, 108 metabolites and 91 enzymes across 1246 human gut bacterial species and 88 mouse gut bacterial species. Users can browse, search, and highlight the tryptophan metabolic pathway, as well as predict tryptophan metabolites on the basis of a given taxonomy profile using a Bayesian logistic regression model. We validated our approach using two gut microbiome metabolomics studies and demonstrated that TrpNet was able to better predict alterations in in indole derivatives compared to other established methods.
Background:
The construction of fused heterocyclic compounds is always fascinating on the strength of their applications as novel pharmaceuticals. Multi-component reactions (MCRs) are atom economical, beneficial, straightforward and ecofriendly approach for synthesis of complex heterocycles in a single step with higher selectivity.
Methods:
The review mainly focused on the synthesis of fused heterocycles such as pyrimidine - chromene, Pyrrolo - pyrazine, Pyrazolo - pyrimidine, pyran - imidazole and pyrazole- imidazole - pyrimidine, pyran - pyridmidone, pyrrolo - chromene, pyridine-pyrimidinone, fused indole derivatives, furano - pyran along with some simple MCRs discussed, which published in in the period of 2019 and 2020. A table of summary about 50 heterocycles with product, catalysts and cited literature for are given at end.
Conclusions:
From this review we understand that MCRs can deliver an effortless access to molecular targets of our interest with wide choice of reactants and their combinations. Thus, the creativity and choice of reactants are pushing the development in MCRs towards more atom economical and eco-friendly approach
Objective:
Understanding recent trends in the development of MCRs is a requisite for anyone, who wish to synthesise simple and fused heterocycles. By keeping this as primary objective, the present review provides an overview of latest developments in fused heterocyclic synthesis via green multicomponent reactions in the period of 2019 and 2020.
The primary purpose of this research work is to synthesize, characterize and biological evaluation of novel pyrazoline fused indole derivatives lead to creating a new molecular frame work.
Methodology: In the present study, the new series of novel pyrazoline fused indole derivatives were synthesized from from indole and substituted acetophenone by the 4 step process. In the first step indole and dimethyl formamide were coupled by using phosphorous oxychloride and NaOH to prepare the compound 1 Indole-3-aldehyde. In the second step compound 1 was condensed with substituted aetophenone to synthesis the compound 2 chalcones (a-h). In the third step chalcones 2(a-h) were coupled with semicarbazide or thiosemicarbazide to synthesis the compound 3(a-p). In the final step compound 3(a-p) were coupled with indole-3-aldehyde to prepare the final product of R-substitutedN-((1H-indol-3-yl)methylene)-5-(1H-indol-3-yl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide and R-substitutedN-((1H-indol-3-yl)methylene)-5-(1H-indol-3-yl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide 4(a-p).
Results: The chemical structures of the synthesized compounds were characterized by means of IR, Mass and NMR spectroscopy. The compounds were screened for anti-diabetic activity by In-vitro and In-vivo methods. In In-vivo method 4a, 4m have exhibited moderate anti-diabetic activity as that of standard drug, glibenclamide. In In-vitro method 4a, 4e & 4m have shows moderate anti-diabetic activity as that of reference standard, acarbose.
Conclusion: The synthesized novel pyrazoline fused indole derivatives have moderate antidiabetic activity as that of standard drug by In-vitro and In-vivo methods. These compounds can be further exploited to get the potent lead compound.
Crystallographic structure, activity prediction, and hydrogen bonding analysis of some CSD-based 3,3'-bis-indole derivatives: A review