On the traditional medicinal plants and plant-derived natural drugs used by indigenous people of Nagaland, India

An ethnobotanical documentation on the medicinal plants used by local people of Nagaland (North-east India) has been presented here. The study explored 33 plant species (with their local names, indigenous applications, sources/origins, parts of plants used, bioactive compounds present, process of preparing medicines from the plants) belonging to 28 families have been reviewed thoroughly. Some examples are, Catharanthus roseus (Tsuinrinaro, Periwinkle), Acacia pennata (Chakrangaing, Ballikhadira), Adhatoda vasica (Kicharangnaro, Malabar-nut), Ageratum conzyoides (Imchenriza, Billy-goat-weed,/Tropical-white-weed), Alstonia scholaris (Lazarongpang, Blackboard), Rauvolfia serpentina (Per-mozutong, Indian-snakeroot), etc. Plant based drugs are very popular and effective in Nagaland from ancient times but thorough-documentation with scientific-background of effectiveness, active chemical-compounds present, their action-mechanism, etc., are still scanty. Such review can be of useful for pharmacologist, phyto-chemists to a broad group of researchers and may lead to discovery of new sources of novel medicines through traditional therapeutic knowledge.</p

Structural Insight into Groove Binding of Yohimbine with Calf Thymus DNA: A Spectroscopic, Calorimetric, and Computational Approach

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 105 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

Conformational Flexibility Influences Degree of Hydration of Nucleic Acid Hybrids

Four nucleic acid duplexesDNA/RNA hybrid, RNA/DNA hybrid, RNA duplex, and DNA duplexwere studied under molecular crowding conditions of osmolytes. Destabilization of duplexes (ΔΔG°25) indicated that the ΔΔG°25 values of hybrids were intermediate between those of DNA and RNA duplexes. In the presence of polyethylene glycol 200, the ΔΔG°25 values were estimated to be +3.0, +3.5, +3.5, and +4.1 kcal mol–1 for the DNA duplex, DNA/RNA hybrid, RNA/DNA hybrid, and RNA duplex, respectively. Differences in the number of water molecules taken up (−Δnw) upon duplex formations between 0 and 37 °C (Δ(−Δnw)) were estimated to be 44.8 and 59.7 per duplex structure for the DNA/RNA and RNA/DNA hybrids, respectively. While the Δ(−Δnw) value for the DNA/RNA hybrid was intermediate between those of the DNA (26.1) and RNA (59.2) duplexes, the value for RNA/DNA hybrid was close to that of RNA duplex. These differences in the thermodynamic parameters and hydration are probably a consequence of the enhanced global flexibility of the RNA/DNA hybrid structure relative to the DNA/RNA hybrid structure observed in molecular dynamics simulations. This molecular crowding study provides information not only on hydration but also on the flexibility of the conformation of nucleic acid duplexes

Effect of Locked Nucleic Acid Modifications on the Thermal Stability of Noncanonical DNA Structure

We studied the kinetic and thermodynamic effects of locked nucleic acid (LNA) modifications on parallel and antiparallel DNA duplexes. The LNA modifications were introduced at cytosine bases of the pyrimidine strand. Kinetic parameters evaluated from melting and annealing curves showed that the association and dissociation rate constants for the formation of the LNA-modified parallel duplex at 25.0 °C were 3 orders of magnitude larger and 6 orders of magnitude smaller, respectively, than that of the unmodified parallel duplex. The activation energy evaluated from the temperature-dependent rate constants was largely altered by the LNA modifications, suggesting that the LNA modifications affected a prenucleation event in the folding process. Moreover, thermodynamic parameters showed that the extent of stabilization by the LNA modification for parallel duplexes (3.6 kcal mol–1 per one modification) was much more significant than that of antiparallel duplexes (1.6 kcal mol–1). This large stabilization was due to the decrease in ΔH° that was more favorable than the decrease in TΔS°. These quantitative parameters demonstrated that LNA modification specifically stabilized the noncanonical parallel duplex. On the basis of these observations, we succeeded to stabilize the parallel duplex by LNA modification at the physiological pH. These results can be useful in the rational design of functional molecules such as more effective antisense and antigene strands, more sensitive strands for detection of target DNA and RNA strands, and molecular switches responding to solution pH

Biophysical and molecular modeling evidences for the binding of sulfa molecules with hemoglobin

The molecular mechanism of the heme protein, hemoglobin (Hb) interaction with sulfa molecule, sulfadiazine (SDZ) has been investigated through spectroscopic, neutron scattering and molecular modeling techniques. Absorption and emission spectroscopic studies showed that SDZ molecules were bound to Hb protein, non-cooperatively. The binding affinityof SDZ-Hb complex at standard experimental condition was evaluated to be around (4.2 ± 0.07) ×104, M−1with 1:1 stoichiometry. Drug induced structural perturbation of the 3 D protein moiety was confirmed through circular dichroism (CD), synchronous fluorescence and small angle neutron scattering methods. From the temperature dependent spectrofluorometric studies, the negative standard molar Gibbs energy change suggested the spontaneity of the reaction. The negative enthalpy and positive entropy change(s) indicated towards the involvement of both electrostatic and hydrophobic forces during the association process. Salt dependent fluorescence study revealed major contributions from non-poly-electrolytic forces. Molecular modeling studies determined the probable binding sites, types of interaction involved and the conformational alteration of the compactness of the Hb structure upon interaction with SDZ molecule. Overall, the study provides detailed insights into the binding mechanism of SDZ antibiotics to Hb protein. Communicated by Ramaswamy H. Sarma</p

Heme Protein Binding of Sulfonamide Compounds: A Correlation Study by Spectroscopic, Calorimetric, and Computational Methods

Protein–ligand interaction studies are useful to determine the molecular mechanism of the binding phenomenon, leading to the establishment of the structure–function relationship. Here, we report the binding of well-known antibiotic sulfonamide drugs (sulfamethazine, SMZ; and sulfadiazine, SDZ) with heme protein myoglobin (Mb) using spectroscopic, calorimetric, ζ potential, and computational methods. Formation of a 1:1 complex between the ligand and Mb through well-defined equilibrium was observed. The binding constants obtained between Mb and SMZ/SDZ drugs were on the order of 104 M–1. SMZ with two additional methyl (−CH3) substitutions has higher affinity than SDZ. Upon drug binding, a notable loss in the helicity (via circular dichroism) and perturbation of the three-dimensional (3D) protein structure (via infrared and synchronous fluorescence experiments) were observed. The binding also indicated the dominance of non-polyelectrolytic forces between the amino acid residues of the protein and the drugs. The ligand–protein binding distance signified high probability of energy transfer between them. Destabilization of the protein structure upon binding was evident from differential scanning calorimetry results and ζ potential analyses. Molecular docking presented the best probable binding sites of the drugs inside protein pockets. Thus, the present study explores the potential binding characteristics of two sulfonamide drugs (with different substitutions) with myoglobin, correlating the structural and energetic aspects