ABSTRACT
Four different hybrid compounds have been efficiently synthesized by conjugation of deacetylthiocolchicine with pironetin-inspired derivatives. The modest bioactivity and the apparent absence of interaction with α-tubulin is explained by a posteriori in silico investigation, which suggests a relevant distance between the thiocolchicine binding site and the proper pocket on the α-tubulin. The modest activity on resistant cells suggested that the lipophilic nature of the linker used renders the resulting compounds better substrates for p-Gp efflux pumps. The study better clarifies the design of bivalent compounds that target hetero tubulin/microtubules.
Subject(s)
Antineoplastic Agents/chemical synthesis , Colchicine/analogs & derivatives , Tubulin/metabolism , Antineoplastic Agents/pharmacology , Binding Sites , Cell Line, Tumor , Cell Proliferation/drug effects , Colchicine/chemistry , Colchicine/metabolism , Humans , Ligands , Molecular Dynamics Simulation , Stereoisomerism , Tubulin/chemistryABSTRACT
Correction for 'Self-assembled 4-(1,2-diphenylbut-1-en-1-yl)aniline based nanoparticles: podophyllotoxin and aloin as building blocks' by Gaia Fumagalli, et al., Org. Biomol. Chem., 2017, DOI: 10.1039/c6ob02591a.
ABSTRACT
The ability of 4-(1,2-diphenylbut-1-en-1-yl)aniline as a self-assembly inducer is reported. The conjugation of this moiety with aloin or podophyllotoxin resulted in spherical nanoparticles that were characterized by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) and NanoSight technology. A preliminary biological evaluation on two cancer cell lines is reported.
ABSTRACT
Self-assembly drug conjugate preparation is a promising approach to improve activity and penetration through physiological barriers of potent small molecules, as well as to reduce any side effects. Drug conjugates can self-assemble in water to form nanoparticles (NPs) that offer several advantages because: (i) they are easy to obtain; (ii) they can reach high local drug concentration in tumor tissues; and (iii) they can reduce the side effects of drugs. All these factors improve drug pharmacokinetic properties. Here, we have reviewed the scope of nanotechnology-based self-assembly drug delivery approaches focusing on prodrugs able to form NPs by self-assembly; we have also summarized the current perspective and challenges facing the successful treatment of cancer.
Subject(s)
Antineoplastic Agents , Drug Delivery Systems , Nanoparticles , Neoplasms/drug therapy , Prodrugs , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Humans , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Prodrugs/administration & dosage , Prodrugs/chemistry , Prodrugs/pharmacology , Prodrugs/therapeutic useABSTRACT
A stereocontrolled, facile and high-yield approach for producing (+)-altroDNJ, has been developed starting from the inexpensive commercial cis 2-butene-1,4-diol. Sharpless epoxidation and a subsequent dihydroxylation were used for the introduction of all stereocentres; finally, the ring closure under basic conditions afforded the piperidine heterocycle.
Subject(s)
1-Deoxynojirimycin/analogs & derivatives , 1-Deoxynojirimycin/chemical synthesis , 1-Deoxynojirimycin/chemistry , Epoxy Compounds/chemical synthesis , Heterocyclic Compounds , Hydroxylation , Indicators and Reagents , Molecular Conformation , StereoisomerismABSTRACT
2-Piperidineethanol (1) and its corresponding N-protected aldehyde (2) were used for the synthesis of several natural and synthetic compounds. The existence of a stereocenter at position 2 of the piperidine skeleton and the presence of an easily-functionalized group, such as the alcohol, set 1 as a valuable starting material for enantioselective synthesis. Herein, are presented both synthetic and enzymatic methods for the resolution of the racemic 1, as well as an overview of synthesized natural products starting from the enantiopure 1.
Subject(s)
Alkaloids/chemical synthesis , Chemistry Techniques, Synthetic/methods , Ethanol/analogs & derivatives , Piperidines/chemistry , Biocatalysis , KineticsABSTRACT
The development of modern technologies casts a new light on the natural products as an invaluable source of lead compounds that could guide drug discovery. Cancer stem cells are a subpopulation of cancer cells with a high clonogenic capacity and the ability to reform the parental tumours upon transplantation. They have been proposed to drive tumorigenesis and metastases. In this review, we present the ability of forty-nine different natural products to influence the biology of cancer stem cells.
