5-Aminoisophthalate-based kojic acid-appended bis-1,2,3-triazole: a fluorescent chemosensor for Cu2+ sensing and in silico study.

A new, easy-to-prepare, and highly selective fluorescent chemosensor, i.e., 5-aminoisophthalate-based kojic acid-appended bis-1,2,3-triazole, was synthesized from an alkyne of 5-aminoisophthalic acid and azido-kojic acid using Cu(i)-catalyzed click chemistry and then successfully characterized. The alkyne structure of 5-aminoisophthalic acid, 1, was supported by the single-crystal X-ray crystallographic data. The fluorescent probe 3 was found to be highly selective for Cu2+ ions supported by the Job's plot with a stoichiometric ligand : metal ratio of 2 : 1, exhibiting almost a two-fold enhancement in the emission intensity upon the addition of Cu2+ ions (0-25 µM) with a detection limit of 8.82 µM. A comparison with LODs from previously developed chemosensors for Cu2+ ions was also conducted. Reversibility analysis indicated that probe 3 could be used as both a reusable sensor and as a scavenger of copper ions. DFT calculations with the basis sets B3LYP/6-311G(d,p) and LanL2DZ were employed for geometrical optimizations of structures of the alkyne 1, azide 2, probe 3, and complex 3.Cu2+. Hirshfeld surface analysis revealed significant intermolecular interactions in compound 1. Additionally, molecular docking for the antimicrobial activity showed the better antibacterial efficacy of probe 3.

Dehydroacetic acid a privileged medicinal scaffold: A concise review.

From the last decade, research on dehydroacetic acid (DHA) and its derivatives has increased immensely due to its significant role in various fields, including medicine, cosmetics, food industry, and so on. In the medicinal area, DHA plays an essential role in developing novel action-based drugs, which are helpful for treating various diseases. Besides its plethora of biological applications, its chelating ability offers the easiest synthetic route for synthesizing more active metal complexes. DHA derivatives along with their metal complexes show a number of biological activities and also exhibit various interactions with multiple biological targets. This article summarizes recent medicinal applications (2000-onwards) of DHA-based compounds and their analogs, along with their structure-activity relationship (SAR) analysis. Their interactions with different target enzymes are also discussed. This information derived from SAR analysis would be helpful for medicinal chemists working on the development of drugs based on heterocyclic frameworks, particularly those based on the DHA scaffold.

Nascent pharmacological advancement in adamantane derivatives.

The adamantane moiety has attracted significant attention since its discovery in 1933 due to its remarkable structural, chemical, and medicinal properties. This molecule has a notable impact in the therapeutic field because of its "add-on" lipophilicity to any pharmacophoric moieties. As in the case of molecular hybridization, in which one pharmacophore is attached to another one(s) with a probability of increasing the biological activity, adding an adamantane unit improves the absorption distribution, metabolism and excretion properties of the resultant hybrid molecule. This review summarizes various reports highlighting the biological activities of adamantane-based synthetic compounds and their structure-activity relationship study. The information presented in this review may open up possible dimensions for adamantane-based drug development and discovery in the pharmaceutical industry after proper structural modifications.

Ampyrone appended 1,2,3-triazole as selective fluorescent Cu(II) ion sensor: DFT and docking findings.

The present report describes the application of the 'Click Chemistry' pathway to synthesize a fluorescent probe (APT) based on ampyrone (4-aminoantipyrine), entailing two benzyl groups as the fluorophores coupled to the antipyrine structure through 1,2,3-triazole moieties. Infrared spectroscopy (IR), nuclear magnetic resonance (1H and 13C), and mass spectrometry were the standard spectroscopic methods used to characterize APT. The ion recognition potential of the probe was analyzed through absorption and emission spectroscopy employing a 4:1 combination of CH3CN and H2O, which demonstrated APT to be an efficient sensing agent for Cu(II) ions, wherein the absorption spectrum of the probe displayed a hypsochromic shift with a hyperchromic shift on gradually adding the metal ion solution of Cu(II), whereas quenching of the probe's fluorescence emission on Cu(II) addition was attributed to the chelation-enhanced fluorescence quenching (CHEQ), induced by the d9 electronic configuration of Cu(II). The stoichiometry of the complexation of APT with Cu(II) is indicative of a 1:1 ratio, while the detection limit (LOD) and quantification limit (LOQ) as estimated from the fluorescence titration results were 3.11 µM and 10.35 µM respectively. Furthermore, DFT analysis was also undertaken to yield the energy-optimized structures and HOMO-LUMO density plots of APT and its corresponding Cu(II) complex via the B3LYP/631G+(d,p) level of theory for APT, and LANL2DZ basis set for the APT-Cu(II) complex. Docking analysis of the probe with the synaptic vesicle protein (SV2A) gave glimpses about its anticonvulsant properties.

1,2,3-Triazoles of 8-Hydroxyquinoline and HBT: Synthesis and Studies (DNA Binding, Antimicrobial, Molecular Docking, ADME, and DFT).

A new series of 1,2,3-triazole hybrids containing either 2- or 4-hydroxyphenyl benzothiazole (2- or 4-HBT) and naphthalen-1-ol or 8-hydroxyquinoline (8-HQ) was synthesized in high yields and fully characterized. In vitro DNA binding studies with herring fish sperm DNA (hs-DNA) showed that quinoline- and 2-HBT-linked 1,2,3-triazoles of shorter alkyl linkers such as 6a are better with a high binding affinity (3.90 × 105 L mol-1) with hs-DNA as compared to naphthol- and 4-HBT-linked 1,2,3-triazoles bound to longer alkyl linkers. Molecular docking of most active 1,2,3-triazoles 6a-f showed high binding energy of 6a (-8.7 kcal mol-1). Also, compound 6a displayed considerable antibacterial activity and superior antifungal activity with reference to ciprofloxacin and fluconazole, respectively. The docking results of the fungal enzyme lanosterol 14-α-demethylase showed high binding energy for 6a (-9.7 kcal mol-1) involving dominating H-bonds, electrostatic interaction, and hydrophobic interaction. The absorption, distribution, metabolism, and excretion (ADME) parameter, Molinspiration bioactivity score, and the PreADMET properties revealed that most of the synthesized 1,2,3-triazole molecules possess desirable physicochemical properties for drug-likeness and may be considered as orally active potential drugs. The electrophilicity index and chemical hardness properties were also studied by density functional theory (DFT) using the B3LYP/6-311G(d,p) level/basis set.

Synthesis, antimicrobial potency with in silico study of Boc-leucine-1,2,3-triazoles.

A library of N-Boc protected Leucine-linked 1,4-disubstituted 1,2,3-triazoles was synthesized and fully characterized, in high yield via copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. In vitro antibacterial activity showed that compound 4h found to be more potent than the reference drug Ciprofloxacin (MIC: 0.0196 µmol/mL) against tested bacterial strains S. entrica, B. subtilis, S. aureus, E. coli and P. auroginosa with MIC: 0.0148, 0.0074, 0.0148, 0.0074, and 0.0074 µmol/mL, respectively and antifungal activity with MIC: 0.0148 µmol/mL as compared to reference drug Fluconazole (MIC: 0.0102 µmol/mL) against A. niger and C. albicans fungal strains. Further, the molecular docking study on 4h and its predecessor alkyne 3 by choosing E. coli topoisomerase II, DNA Gyrase (PDB ID: 1KZN) showed better binding with triazole than alkyne and these results were supported by DFT study using B3LYP/6-311G(d,p) basis set.