Synthesis and inverse virtual screening of new bi-cyclic structures towards cancer-relevant cellular targets

Structural Chemistry - We report here synthetic approaches to access new classes of small molecules based on three heterocyclic scaffolds, i.e. 3,7-dihydropyrimido[4,5-d]pyridazine-4,8-dione,...     

Experimental and Theoretical Studies of the Pyrazoline Derivative 5-(4-methylphenyl)-3-(5-methylfuran-2-yl)-1-phenyl-4,5-dihydro-1H-Pyrazole and its Application for Selective Detection of Cd2+ ion as Fluorescent Sensor

A simple fluorescent chemosensor 5-(4-methylphenyl)-3-(5-methylfuran-2-yl)-1-phenyl-4, 5-dihydro-1H-pyrazole (PY) has been synthesized for the detection of Cd²⁺ ion.The fluorescent probe PY shows high selectivity for Cd²⁺in the presence of othermetal ions (Co²⁺, Cu²⁺, Hg²⁺, Mn²⁺, Zn²⁺, Fe³⁺, Pb²⁺, Ni²⁺, and Al³⁺). The fluorescence intensity of the PY has been strongly quenched with increasing concentration of Cd²⁺ (0–0.9 μM)via photoinduced electron transfer mechanism. The binding constant of Cd²⁺ to PY for the 1:1 complex isfound to be 5.3?×?10⁵ M^?1with a detection limit of 0.09 μM. The chemosensor was successfully applied for determination of Cd²⁺ in different water samples (tap, river, and bottled water) showing good recovery values in the range of 94.8–101.7% with RSD less than 3%. Density functional theory (DFT) calculations were also performed to investigate electronic and spectral characteristics which are quite agreeable with the experimental value. The results show that the synthesized fluorescent chemosensor shows good selectivity towards Cd²⁺ and can be readily applied for the detection of Cd²⁺ in real samples including water samples.

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Solid-phase synthesis and biological screening of N-alpha-mercaptoamide template-based matrix metalloprotease inhibitors

A series of N-alpha-mercaptoacetyl containing dipeptides have been prepared on solid-phase supports as putative matrix metalloprotease (MMP) inhibitors. Inhibitor design was based on a positional scanning approach of the amino acids present within a template molecule, previously shown to be an MMP inhibitor with good pharmacological characteristics. This study is the first step in a unique programme, designed to expand the repertoire of molecular templates which can be chosen as starting points for the development of more focused parallel and/or combinatorial libraries of MMP inhibitors as a means to accelerate the lead discovery process. This paper reports the success of such an approach in the development of agents with activity against a number of pathologically important MMPs. After screening of these positional scanning libraries, we have obtained important SAR information, in particular, pharmacophores with the ability to impart selectivity for particular MMP species.     

Bis(thiophen-2-yl-methylene) Benzene-1, 4-Diamine as Fluorescent Probe for the Detection of Fe3+ in Aqueous Samples

Journal of Fluorescence - A Schiff base bis(thiophen-2-yl-methylene)benzene-1, 4-diamine (L) was synthesized and used for selective and sensitive detection of Fe3+. L exhibited enhanced...