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

Abstract

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.

Design and Synthesis of Carbothioamide/Carboxamide-Based Pyrazoline Analogs as Potential Anticancer Agents: Apoptosis, Molecular Docking, ADME Assay, and DNA Binding Studies

“…Titration experiments were repeated three times ( n = 3) to ensure consistent results. The binding affinity ( K b ) was calculated using eq : − where A obsd /[compound], the extinction coefficient of the complex in the bound form, and the extinction coefficient for the complex are represented by absorption coefficients, ε a , ε b , and ε f , respectively.…”

“…Titration experiments were repeated three times (n = 3) to ensure consistent results. The binding affinity (K b ) was calculated using eq 2: 47…”

Synthesis of 1,2,3‐Triazole Tethered Indole Derivatives: Evaluation of Anticancer Activity and Molecular Docking Studies

“…The side-chain substituents helped especially in affixing to the binding site residues by making one H-bond with Ala96 and two halogen bonds with Val93 and His95. [33] These interactions of triazole hybrid indole derivatives with aurora kinase-1, DNA topoisomerase II alpha, accelerates our docking protocol.…”

“…The triazole‐tethered indoles displayed more number of interactions and the introduction of a substituted triazole ring caused better fitting of the compounds. The side‐chain substituents helped especially in affixing to the binding site residues by making one H‐bond with Ala96 and two halogen bonds with Val93 and His95 [33] . These interactions of triazole hybrid indole derivatives with aurora kinase‐1, DNA topoisomerase II alpha, accelerates our docking protocol.…”

1,2,3-Triazole Tethered Hybrid Capsaicinoids as Antiproliferative Agents Active against Lung Cancer Cells (A549)

“…On the other hand, the 1,2,3-triazole moiety is a key pharmacophore exhibiting a wide range of pharmacological activities. ,− The 1,2,3-triazole moiety plays a significant role in medicinal chemistry owing to its capability of forming a hydrogen bond, which improves its solubility and ability to favorably interact with bimolecular targets. − 1,2,3-Triazoles are highly stable to metabolic degradation as compared to other heterocyclic compounds. − Several 1,2,3-triazole tethered natural product scaffolds like oleanolic acid, quinolone, isatin, myrrhanone C, podophyllotoxin, artemisinin, coumarin, and curcumin with a hydrophobic character have demonstrated potential antiproliferative activities against lung cancer cell lines (Figure ). Conjugation of the 1,2,3-triazole moiety evidenced to be one of the important strategies to improve the anticancer properties of natural scaffolds, and many secondary leads have been developed by this approach.…”