Revealing the Improved Binding Interaction of Plant Alkaloid Harmaline with Human Hemoglobin in Molecular Crowding Condition.

Harmaline and harmine are two structurally similar ß-carboline alkaloids with several therapeutic activities, such as anti-inflammatory, antioxidant, neuroprotective, nephroprotective, antidiabetic, and antitumor activities. It has been previously reported that the interaction between harmaline and hemoglobin (Hb) is weak in buffer media compared to harmine. Crowding agents induce a molecular crowding environment in the ex vivo condition, which is almost similar to the intracellular environment. In this present study, we have investigated the nature of the interactions of harmaline and harmine with Hb by increasing the percentage of the crowding agent in buffer solution. The results of the UV-vis and fluorescence spectroscopy analysis have showed that with an increasing proportion of crowding agents, the interaction between harmaline and Hb is steadily improving in comparison to harmine. It has been found that the binding constant of Hb-harmaline reaches 6.82 × 105 M-1 in the 40% polyethylene glycol 200-mediated crowding condition, indicating high affinity compared to very low interaction in buffer media. Steady-state fluorescence anisotropy along with fluorescence lifetime measurements further revealed that the rotational movement of harmaline is maximally restricted by Hb in high crowding environments. Stoichiometry results represent that Hb and harmaline interacts in a 1:1 ratio in different percentages of the crowding agent. The circular dichroism spectroscopic results predict stronger interaction of harmaline with Hb (secondary structure alterations) in a higher crowding environment. From the melting study, it was found that the reactions between Hb and harmaline in crowding environments are endothermic (ΔH > 0) and disordering (ΔS > 0) in nature, indicating that hydrogen bonding and van der Waals interactions are the main interacting forces between Hb and harmaline. Harmaline molecules are more reactive in molecular crowding conditions than in normal buffer condition. This study represents that the interaction between harmaline and Hb is stronger compared to the structurally similar harmine in a molecular crowding environment, which may enlighten the drug discovery process in cell-mimicking conditions.

Multispectroscopic Investigations of the Binding Interaction between Polyethylene Microplastics and Human Hemoglobin.

In this investigation, different multispectroscopic analytical techniques have been used to explore the interaction between polyethylene microplastics (PE-MPs) and human hemoglobin (HHb), an oxygen carrier in the human blood circulatory system. Ultraviolet-visible absorption studies have demonstrated that HHb molecules may interact with PE-MPs, and thermal melting studies have indicated that PE-MPs have a stabilizing effect on HHb. Further circular dichroism and Fourier transform infrared spectroscopic studies have revealed the distinct changes in HHb's secondary structures caused by the formation of the HHb-PE-MP binding complex. These findings imply that PE-MPs could enter the blood circulation system of humans and may be hazardous to humans. This work explains the potential binding interaction of microplastics at the molecular level and offers insight into the intermolecular interaction between PE-MPs and HHb.

Exploring the Structural Importance of the C3=C4 Double Bond in Plant Alkaloids Harmine and Harmaline on Their Binding Interactions with Hemoglobin.

Harmine and harmaline are two structurally similar heterocyclic ß-carboline plant alkaloids with various therapeutic properties, having a slight structural difference in the C3=C4 double bond. In the present study, we have reported the nature of the interaction between hemoglobin (Hb) with harmine and harmaline by employing several multispectroscopic, calorimetric, and molecular docking approaches. Fluorescence spectroscopic studies have shown stronger interaction of harmine with Hb compared to that of almost structurally similar harmaline. Steady-state anisotropy experiments further show that the motional restriction of harmine in the presence of Hb is substantially higher than that of the harmaline-Hb complex. Circular dichroism (CD) study demonstrates no conformational change of Hb in the presence of both alkaloids, but CD study in 1-cm cuvette path length also demonstrates stronger affinity of harmine toward Hb compared to harmaline. From the thermal melting study, it has been found that both harmine and harmaline slightly affect the stability of Hb. From isothermal titration calorimetry (ITC), we have found that the binding process is exothermic and enthalpy driven. Molecular docking studies indicated that both harmine and harmaline prefer identical binding sites in Hb. This study helps us to understand that slight structural differences in harmine and harmaline can alter the interaction properties significantly, and this key information may help in the drug discovery processes.

Structural insights and shedding light on preferential interactions of dietary flavonoids with G-quadruplex DNA structures: A new horizon.

G-quadruplex, a structurally unique structure in nucleic acids present all throughout the human genome, has sparked great attention in therapeutic investigations. Targeting G-quadruplex structure is a new strategy for the drug development. Flavonoids are found in almost all dietary plant-based beverages and food products; therefore, they are ingested in significant proportions through the human diet. Although synthetically developed drug molecules are used vigorously but they have various adverse effects. While on the other hand, nature supplies chemically unique scaffolds in the form of distinct dietary flavonoids that are easily accessible, less poisonous, and have higher bioavailability. Because of their great pharmacological effectiveness and minimal cytotoxicity, such low molecular weight compounds are feasible alternatives to synthetic therapeutic medicines. Therefore, from a drug-development point of view, investigation on screening the binding capabilities of quadruplex-interactive small natural compounds like dietary flavonoids are expected to be highly effective, with a particular emphasis on the selectivity towards polymorphic G-quadruplex structures. In this respect, quadruplexes have scintillated research into their potential interaction with these dietary flavonoids. The purpose of this review is to offer an up-to-date close-up look at the research on their interaction with structurally varied dietary flavonoids with the goal of providing newer perspectives to construct novel therapeutic agents for next-generation disease managements.