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Insights into binding efficacy and thermodynamic aspects of small molecules are important for rational drug designing and development. Here, the interaction of Harmane (Har), a very important bioactive indole alkaloid, with AT and GC hairpin duplexÀDNAs has been reported using various biophysical tools. Detailed molecular mechanism with special emphasis on binding nature, base specificity, and thermodynamics have been elucidated via probing nucleic acids with varying base compositions. Har bound to both the DNA strands exhibited hypochromic effect in absorbance whereas bathochromic and hypochromic effects in fluorescence spectra.The binding constants estimated were in the order of 10 5 M À1 (higher for GC sequence compared with AT) with 1:1 stoichiometry. Noncooperative binding mode has been observed via intercalation in both the cases. The thermodynamic profile was obtained from temperature-dependent fluorescence experiments. Both Har-AT and Har-GC complexations were exothermic in nature associated with positive entropy and negative enthalpy changes. Salt-dependent studies revealed that the binding interaction was governed by nonpolyelectrolytic and hydrophobic interaction forces. The ligand-induced structural perturbation of the DNA structures was evident from the circular dichroism data. Molecular modelling data indicated towards the involvement of hydrophobic forces and hydrogen bonding.

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Even today, talking about sexual dysfunction largely remains a taboo. Therefore less studies have been recorded and fewer remedies given. Erectile dysfunction (ED) is one of the most commonly treated psychological disorders that leads to major distress, interpersonal limitation and reduces the quality of life and marriage. This study aimed to assess a plant‐derived molecule, yohimbine (Yoh; a β‐carboline indole alkaloid often used for ED treatment) and its potential binding phenomenon with haemoglobin (Hb). Successful binding of Yoh with Hb is evident from spectroscopic and molecular‐docking results. Yoh quenched the fluorescence of Hb efficiently through a static mode. The binding affinity was in the order of 105 M−1 with 1:1 stoichiometry. Thermodynamic analyses concluded that the protein–ligand association was spontaneous and was attributed to entropy‐driven exothermic binding. Nonpolyelectrolytic factor was the core, dominating factor. Structural aspects were deciphered through infrared spectroscopy and computational methods. The giant 3D‐protein moiety was significantly perturbed through drug binding. Hydrophobic forces and hydrogen bonding participation were stipulated by molecular modelling data. This study reveals the detailed interaction pattern and molecular mechanism of Hb–Yoh binding, correlating the structure–function relationship for the first time, and therefore holds enormous importance from the standpoint of rational and efficient drug design and development.

A variety of anticancer and antibacterial drugs target DNA as one of their primary intracellular targets. Understanding ligand−DNA interactions and developing new, promising bioactive molecules for clinical use are greatly aided by elucidating the interaction between small molecules and natural polymeric DNAs. Small molecules′ ability to attach to and inhibit DNA replication and transcription provides more information on how drugs impact the expression of genes. Yohimbine has been broadly studied in pharmacological properties, while its binding mode to DNA has not been explicated so far. In this study, an attempt was made to explore the interaction between Yohimbine (YH) and calf thymus (CT-DNA) by using varying thermodynamics and in silico approaches. Minor hypochromic and bathochromic shifts of fluorescence intensity were observed, suggesting the binding of YH to CT-DNA. The Scatchard plot analysis using the McGhee−von Hipple method revealed noncooperative binding and affinities in the range of 10 5 M −1 . The binding stoichiometry value is 2:1 (2 molecules of YH were span by 1 base pair) and was determined by Job's plot. The thermodynamic parameters suggested exothermic binding, which was favored by negative enthalpy and positive entropy changes from both isothermal titration calorimetry and temperature-dependent fluorescence experiment. Salt-dependent fluorescence suggested that the interaction between the ligand and DNA was governed by nonpolyelectrolytic forces. Kinetics experiment confirmed the static type of quenching. The results of iodide quenching, urea denaturation assay, dye displacement, DNA melting, and in silico molecular docking (MD) suggested groove binding of YH to CT-DNA. Circular dichroism spectra confirmed minimal perturbation of CT-DNA with YH binding via groove region. Therefore, the groove binding mechanism of interaction was validated by biophysical techniques and in silico, MD approaches. The findings supported here may contribute to the development of new YH therapeutics possessing better efficacy and lesser side effects.

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