Robust, universal biomarker assay to detect senescent cells in biological specimens.

Cellular senescence contributes to organismal development, aging, and diverse pathologies, yet available assays to detect senescent cells remain unsatisfactory. Here, we designed and synthesized a lipophilic, biotin-linked Sudan Black B (SBB) analogue suitable for sensitive and specific, antibody-enhanced detection of lipofuscin-containing senescent cells in any biological material. This new hybrid histo-/immunochemical method is easy to perform, reliable, and universally applicable to assess senescence in biomedicine, from cancer research to gerontology

One-step rapid tracking and isolation of senescent cells in cellular systems, tissues, or animal models via GLF16

Identification and isolation of senescent cells is challenging, rendering their detailed analysis an unmet need. We describe a precise one-step protocol to fluorescently label senescent cells, for flow cytometry and fluorescence microscopy, implementing a fluorophore-conjugated Sudan Black-B analog, GLF16. Also, a micelle-based approach allows identification of senescent cells in vivo and in vitro, enabling live-cell sorting for downstream analyses and live in vivo tracking. Our protocols are applicable to cellular systems, tissues, or animal models where senescence is present. For complete details on the use and execution of this protocol, please refer to Magkouta et al.</p

THE DESIGN AND SYNTHESIS OF NEW PYRETHROIDS

THE MANIFESTATION OF PYRETHROID ACTION IS DEPENDENT ON THE PRESENCE OF CERTAIN STRUCTURE FEATURES AT SUITABLE ARRANGEMENT TO THE MOLECULE. A MODEL OF A PYRETHROID MOLECULE IS PROPOSED WHICH CONSISTS OF A MIDDLE PART MADE UP OF AN ESTER GROUP OR ANOTHER ISOSTERIC GROUP, WHICH IS CONNECTED TO A SUBSTITUTED OR UNSUBSTITUTED METHYLENE GROUP AND A GEM-DIMETHYL GROUP OR ANOTHER EQUIVALENT GROUP PLACED IN B POSITITON TO THE ESTER GROUP, AND OF TWO UNSATURATED CENTRES BOUND ON EITHER SIDE OF THE MOLECULE, AT SUITABLE DISTANCES FROM THE ESTER GROUP. FOR THE INVESTIGATION OF THE NECESSITY AND THE FUNCTIONAL ROLE OF THE GROUPS OF THE MODEL PROPOSED, THE FOLLOWING TWO GROUPS OF PYRETHROIDS WERE PLANNED AND PREPARED: 1) CHRYSANTHEMUM MONOCARBOXYLIC ACID ESTERS WITH A- SUBSTITUTED PIPERONYL ALCOHOLS, WHICH WERE PREPARED BY THE REACTION OF THE SUITABLE GRIGNARD REAGENTS (CH3(R)C=CHCH2CH2MGBR,R:ME, ET,N-R,PH) WITH PIPERONAL. 2) BENZYLETHERS OF THE OXIMES OF INDANONE, FLUORENONE, 2- METHYLINDANONE AND 2,2-DIMETHYLINDANONE WHICH WERE PREPARED BY THE REACTION OF THE SUITABLE SUBSTITUTED BENZYLCHLORIDES (C1CH2C6H5R, R:F,CL, CLCH2C6H4R1R2,R1:R2:CL) WITH THE OXIMES SODIUM SALTS. THE RELATIVE LIPOPHILICITY OF THE PRODUCTS WAS DETERMINED ACCORDING TO THE METHOD INTRODUCED BY BRIGGS, USING BIORESMETHRIN AS INTERNAL REFERENCE STANDARD. THA CARBAMIC ACID OXIME ESTERS OF INDANONE AND FLUORENONE WERE ALSO PREPARED BY THE REACTION OF THE SUITABLE ISOCYANATES (RN=C=O. R:ME,ET,ISO-PR) WITH THE OXIMES, IN ORDER TO INVESTIGATE THE VIEW THAT PYRETHROIDS MAY POSSESS CHOLINERGIC ACTION.Η ΕΚΔΗΛΩΣΗ ΤΗΣ ΔΡΑΣΗΣ ΤΩΝ ΠΥΡΕΘΡΟΕΙΔΩΝ ΕΞΑΡΤΑΤΑΙ ΑΠΟ ΤΗΝ ΠΑΡΟΥΣΙΑ ΣΤΟ ΜΟΡΙΟ ΟΡΙΣΜΕΝΩΝ ΔΟΜΙΚΩΝ ΧΑΡΑΚΤΗΡΙΣΤΙΚΩΝ ΣΕ ΚΑΤΑΛΛΗΛΗ ΔΙΑΤΑΞΗ. ΠΡΟΤΕΙΝΕΤΑΙ ΠΡΟΤΥΠΟ ΤΟΥ ΜΟΡΙΟΥ ΤΩΝ ΠΥΡΕΘΡΟΕΙΔΩΝ ΤΟ ΟΠΟΙΟ ΑΠΟΤΕΛΕΙΤΑΙ ΑΠΟ ΤΟ ΕΝΔΙΑΜΕΣΟ ΤΜΗΜΑ ΠΟΥ ΠΕΡΙΛΑΜΒΑΝΕΙ ΜΙΑ ΕΣΤΕΡΟΜΑΔΑ 'Η ΑΛΛΗ ΙΣΟΣΤΕΡΗ ΟΜΑΔΑ ΠΟΥ ΣΥΝΔΕΕΤΑΙ ΜΙΑ ΥΠΟΚΑΤΕΣΤΗΜΕΝΗ 'Η ΜΗ ΜΕΘΥΛΕΝΟΜΑΔΑ ΚΑΙ ΜΙΑ GEM-ΔΙΜΕΘΥΛΟΜΑΔΑ 'Η ΑΛΛΗ ΙΣΟΔΥΝΑΜΗ ΟΜΑΔΑ ΣΕ ΘΕΣΗ Β ΩΣ ΠΡΟΣ ΤΗΝ ΕΣΤΕΡΟΜΑΔΑ, ΚΑΘΩΣ ΚΑΙ ΑΠΟ ΔΥΟ ΚΕΝΤΡΑ ΑΚΟΡΕΣΤΟΤΗΤΑΣ ΣΤΑ ΑΚΡΑ ΤΟΥ ΜΟΡΙΟΥ ΣΕ ΚΑΤΑΛΛΗΛΕΣ ΑΠΟΣΤΑΣΕΙΣ ΑΠΟ ΤΗΝ ΕΣΤΕΡΟΜΑΔΑ. ΓΙΑ ΤΗ ΔΙΕΡΕΥΝΗΣΗ ΤΗΣ ΑΝΑΓΚΑΙΟΤΗΤΑΣΚΑΙ ΤΟΥ ΛΕΙΤΟΥΡΓΙΚΟΥ ΡΟΛΟΥ ΤΩΝ ΟΜΑΔΩΝ ΤΟΥ ΠΡΟΤΥΠΟΥ ΑΥΤΟΥ, ΣΧΕΔΙΑΣΤΗΚΑΝ ΚΑΙ ΠΑΡΑΣΚΕΥΑΣΤΗΚΑΝ ΔΥΟ ΚΑΤΗΓΟΡΙΕΣ ΠΥΡΕΘΡΟΕΙΔΩΝ. 1) ΕΣΤΕΡΕΣ ΤΟΥ ΧΡΥΣΑΝΘΕΜΙΚΟΥ ΟΞΕΟΣ ΜΕΑ- ΥΠΟΚΑΤΕΣΤΗΜΕΝΕΣ ΠΙΠΕΡΟΝΥΛΙΚΕΣ ΑΛΚΟΟΛΕΣ ΟΙ ΟΠΟΙΕΣ ΛΗΦΘΗΚΑΝ ΜΕ ΤΗΝ ΕΠΙΔΡΑΣΗ ΤΩΝ ΚΑΤΑΛΛΗΛΩΝ ΑΝΤΙΔΡΑΣΤΗΡΙΩΝ GRIGNARD (CH3(R)C=CHCH2 CH2MGBR, R:ME,ET,N-PR,PH) ΕΠΙ ΤΗΣ ΠΙΠΕΡΟΝΑΛΗΣ. 2) ΒΕΝΖΥΛΑΙΘΕΡΕΣ ΤΩΝ ΟΞΙΜΩΝ ΤΗΣ ΙΝΔΑΝΟΝΗΣ, ΤΗΣ ΦΛΟΥΟΡΕΝΟΝΗΣ, ΤΗΣ 2-ΜΕΘΥΛΟΙΝΔΑΝΟΝΗΣ ΚΑΙ ΤΗΣ 2,2-ΔΙΜΕΘΥΛΟΙΝΔΑΝΟΝΗΣ, ΟΙ ΟΠΟΙΟΙ ΛΗΦΘΗΚΑΝ ΜΕ ΤΗΝ ΕΠΙΔΡΑΣΗ ΤΩΝ ΚΑΤΑΛΛΗΛΩΝ ΒΕΝΖΥΛΟΧΛΩΡΙΔΙΩΝ (CICH2C6H5R, R:F,CI,CICH2C6H4R1R2, R1:R2:C1) ΣΤΑ ΜΕΤΑ ΝΑΤΡΙΟΥ ΑΛΑΤΑ ΤΩΝ ΟΞΙΜΩΝ . ΠΡΟΣΔΙΟΡΙΣΤΗΚΕ Η ΣΧΕΤΙΚΗ ΛΙΠΟΦΙΛΙΚΟΤΗΤΑ ΤΩΝ ΠΡΟΙΟΝΤΩΝ ΩΣ ΠΡΟΣ ΤΗΝ BIORESMETHRIN ΣΥΜΦΩΝΑ ΜΕ ΤΗ ΜΕΘΟΔΟ ΤΟΥ BRIGGS.ΠΑΡΑΣΚΕΥΑΣΤΗΚΑΝ ΕΠΙΣΗΣ ΚΑΡΒΑΜΙΔΙΚΟΙ ΕΣΤΕΡΕΣ ΤΩΝ ΟΞΙΜΩΝ ΤΗΣ ΙΝΔΑΝΟΝΗΣ ΚΑΙ ΤΗΣ ΦΛΟΥΟΡΕΝΟΝΗΣ ΜΕ ΤΗΝ ΕΠΙΔΡΑΣΗ ΤΩΝ ΚΑΤΑΛΛΗΛΩΝ ΙΣΟΚΥΑΝΙΚΩΝ ΑΛΚΥΛΙΩΝ (RN=C=O, R:ME,ET,ISO-PR) ΕΠΙ ΤΩΝ ΟΞΙΜΩΝ, ΠΡΟΚΕΙΜΕΝΟΥ ΝΑ ΔΙΕΡΕΥΝΗΘΕΙ Η ΑΠΟΨΗ ΟΤΙ ΤΑ ΠΥΡΕΘΡΟΕΙΔΗΠΑΡΟΥΣΙΑΖΟΥΝ ΧΟΛΙΝΕΡΓΙΚΗ ΔΡΑΣΗ

Synthesis of New Imidazopyridine Nucleoside Derivatives Designed as Maribavir Analogues

The strong inhibition of Human Cytomegalovirus (HCMV) replication by benzimidazole nucleosides, like Triciribine and Maribavir, has prompted us to expand the structure-activity relationships of the benzimidazole series, using as a central core the imidazo[4,5-b]pyridine scaffold. We have thus synthesized a number of novel amino substituted imidazopyridine nucleoside derivatives, which can be considered as 4-(or 7)-aza-d-isosters of Maribavir and have evaluated their potential antiviral activity. The target compounds were synthesized upon glycosylation of suitably substituted 2-aminoimidazopyridines, which were prepared in six steps starting from 2-amino-6-chloropyridine. Even if the new compounds possessed only a slight structural modification when compared to the original drug, they were not endowed with interesting antiviral activity. Even so, three derivatives showed promising cytotoxic potential.status: publishe

Novel Substituted Purine Isosteres: Synthesis, Structure-Activity Relationships and Cytotoxic Activity Evaluation

A number of pyrrolo[2,3-c]pyridines, pyrrolo[3,2-d]pyrimidines and pyrazolo[4,3-d]pyrimidines were designed and synthesized as antiproliferative agents. The target compounds possessed selected substituents in analogous positions on the central scaffold that allowed the extraction of interesting SARs. The cytotoxic activity of the new derivatives was evaluated against prostatic (PC-3) and colon (HCT116) cell lines, and the most potent analogues showed IC50 values in the nM to low &micro;M range, while they were found to be non-toxic against normal human fibroblasts (WI-38). Flow cytometric analysis of DNA content revealed that the most promising derivative 14b caused a statistically significant accumulation of PC-3 cells at G2/M phase and induced apoptosis in PC-3 cells

Synthesis, Biological Evaluation and Stability Studies of Some Novel Aza-Acridine Aminoderivatives

Several new amino-substituted aza-acridine derivatives bearing a basic side chain have been designed and synthesized. The antiproliferative activity of the target compounds has been evaluated against three cancer cell lines&mdash;namely HCT-116 (colorectal), the uterine sarcoma MES-SA, and its doxorubicin-resistant variant MES-SA/Dx5. A limited number of the new acridines showed marginal cytotoxicity against the tested cell lines; nevertheless, these analogues possessed a similar substitution pattern. The moderate biological activity of these derivatives was attributed to their instability in aqueous media, which has been studied by mass spectrometry and computational chemistry experiments at the density functional level of theory (DFT)