Insights on the comparative affinity of ribonucleic acids with plant-based beta carboline alkaloid, harmine: Spectroscopic, calorimetric and computational evaluation.

Small molecules as ligands target multifunctional ribonucleic acids (RNA) for therapeutic engagement. This study explores how the anticancer DNA intercalator harmine interacts various motifs of RNAs, including the single-stranded A-form poly (rA), the clover leaf tRNA, and the double-stranded A-form poly (rC)-poly (rG). Harmine showed the affinity to the polynucleotides in the order, poly (rA) > tRNA > poly (rC)·poly (rG).

Natural Compounds as Protease Inhibitors in Therapeutic Focus on Cancer Therapy.

Proteases are implicated in every hallmark of cancer and have complicated functions. For cancer cells to survive and thrive, the process of controlling intracellular proteins to keep the balance of the cell proteome is essential. Numerous natural compounds have been used as ligands/ small molecules to target various proteases that are found in the lysosomes, mitochondria, cytoplasm, and extracellular matrix, as possible anticancer therapeutics.

A mini review on human serum albumin - natural alkaloids interaction and its role as drug carrier.

Human serum albumin (HSA) is one of the main protein components of the circulatory system. It's well characterized physiological role is to carry numerous ligands to their target site. Overall pharmacokinetic profile of a drug is deliberately influenced by its affinity towards plasma proteins, especially with albumins.

Exploring spatiotemporal dynamics of flower visitor association pattern on two Avicennia mangroves: a network approach.

Plant-flower visitor interaction is one of the most important relationships regarding the co-existence of the floral and faunal communities. The implication of network approaches is an efficient way to understand the impact of community structure on ecosystem functionality. To understand the association pattern of flower visitors, we performed this study on Avicennia officinalis and Avicennia marina mangroves from the islands of Indian Sundarban over three consecutive years.

Evaluation of therapeutic role of harmaline: cytotoxicity targeting nucleic acids.

Use of small molecules as valuable drugs against diseases is still an indefinable purpose due to the lack of in-detail knowledge regarding proper bio-target identification, specificity aspects, mode-mechanism of binding and proper study. Harmaline, an important beta-carboline alkaloid, shows effective anti-proliferative action against different types of human cancers and is also found to be a nucleic acid targeting natural molecule. This review sought to address the different signal pathways of apoptosis by harmaline in different cancer cell lines and simultaneously to characterize the structure activity aspects of the alkaloid with different motifs of nucleic acid to show its preference, biological efficacy and genotoxicity.

A Mini Review on Molecules Inducing Caspase-Independent Cell Death: A New Route to Cancer Therapy.

Most anticancer treatments trigger tumor cell death through apoptosis, where initiation of proteolytic action of caspase protein is a basic need. But under certain circumstances, apoptosis is prevented by the apoptosis inhibitor proteins, survivin and Hsp70. Several drugs focusing on classical programmed death of the cell have been reported to have low anti-tumorogenic potency due to mutations in proteins involved in the caspase-dependent programmed cell death with intrinsic and extrinsic pathways.

RGS7-ATF3-Tip60 Complex Promotes Hepatic Steatosis and Fibrosis by Directly Inducing TNFα.

The pathophysiological mechanism(s) underlying non-alcoholic fatty liver disease (NAFLD) have yet to be fully delineated and only a single drug, peroxisome proliferator-activated receptor (PPAR) α/γ agonist saroglitazar, has been approved. Here, we sought to investigate the role of Regulator of G Protein Signaling 7 (RGS7) in hyperlipidemia-dependent hepatic dysfunction. RGS7 is elevated in the livers of NAFLD patients, particularly those with severe hepatic damage, pronounced insulin resistance, and high inflammation.

Island Based Assemblage Pattern and Foraging Profile of Insect Flower Visitors on Aegialitis rotundifolia -a Near Threatened Mangrove Plant from Indian Sundarban.

Understanding the association pattern and foraging behaviour of flower visitors is crucial to determine their role in the interaction with plants. To analyse the insect flower visitor association as well as their foraging profile on Aegialitis rotundifolia Roxb.-a near threatened mangrove plant, present study has been conducted among four islands of Indian Sundarban for three consecutive years.

Structure-activity insights of harmine targeting DNA, ROS inducing cytotoxicity with PARP mediated apoptosis against cervical cancer, anti-biofilm formation and therapeutic study.

Harmine exhibits pH dependent structural equilibrium and possesses numerous biological and pharmacological activities. Mode and mechanism of DNA binding and its cytotoxicity were studied by multiple spectroscopic, calorimetric, molecular docking and apoptotic as well as biochemical and histological studies. It exists as cationic (structure I) and decationic form (structure II) in the pH range 3.

Synthetic carboline compounds targeting protein: biophysical and biological perspective.

Pictet-Spengler cyclization method has been adopted for the synthesis of three carboline derived compounds: two compounds with tetrahydro gama- and beta-having CF group and amino alkyl chain at delta and alpha position, respectively, and another with guanidine alkyl chain at alpha-position. Structure-activity relationship of the analogues with human serum albumin was studied by fluorescence and Fourier-transform infrared spectroscopy  followed by molecular docking. The data showed maximum affinity of human serum albumin with comp7 (S0-820) followed by comp3 (S0-1040) and least with comp1 (S0-728).

Carbon dots derived from lychee waste: Application for Fe ions sensing in real water and multicolor cell imaging of skin melanoma cells.

Exploit of biomass as an inexhaustible resource has accepted much more curiosity to the present research world. Herein, a simple, one-step solvothermal action has been used to synthesize an ascendable amount of fluorescent carbon dots (CDs) with an average size of~3.13 nm, from Low-reasonable and green source lychee waste.

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA.

An alternate synthetic route to the important anticancer drug suberoylanilide hydroxamic acid (SAHA) from its α,ß-didehydro derivative is described. The didehydro derivative is obtained through a cross metathesis reaction between a suitable terminal alkene and -benzyloxyacrylamide. Some of the didehydro derivatives of SAHA were preliminarily evaluated for anticancer activity towards HeLa cells.

relationship between serum protein binding to beta-carboline alkaloids: a comparative cytotoxic, spectroscopic and calorimetric assays.

The work highlighted interaction of harmalol, harmaline and harmine with human serum albumin by biophysical and biochemical assays. Presence of serum protein in the media negatively affects the cytotoxicity of the alkaloids. MTT assay indicates concentration-dependent growth inhibitory effect of the alkaloids on A375, MDA-MB-231, HeLa, A549, ACHN and HepG cell, having maximum cytotoxicity with GI value of 6.

Trifluoromethylated carboline compounds targeting DNA: Synthesis, binding and anti-proliferative effects on human cancer cell lines.

Three sets of carboline derived compounds were prepared by Pictet-Spengler cyclization. These tetrahydro β- and γ-carbolines have CF group with an additional amino alkyl chains (α- or δ-position) and guanidine alkyl chains (α-position), of varying length. Structure-activity relationship of these molecules with calf thymus DNA was emphasized by fluorescence, ITC, FTIR and viscosity.

Binding affinity and in vitro cytotoxicity of harmaline targeting different motifs of nucleic acids: An ultimate drug designing approach.

The work focuses towards interaction of harmaline, with nucleic acids of different motifs by multispectroscopic and calorimetric techniques. Findings of this study suggest that binding constant varied in the order single-stranded (ss) poly(A) > double-stranded calf thymus (CT) DNA > double-stranded poly(G)·poly(C) > clover leaf tRNA . Prominent structural changes of ss poly(A), CT DNA, and poly(G)· poly(C) with concomitant induction of optical activity in the bound achiral alkaloid molecule was observed, while with tRNA , very weak induced circular dichroism perturbation was seen.

Therapeutic Role of Harmalol Targeting Nucleic Acids: Biophysical Perspective and in vitro Cytotoxicity.

Background: Harmalol, a beta carboline alkaloid, shows remarkable importance in the contemporary biomedical research and drug discovery programs. With time, there is emerging interest in search for better anti-cancer drugs of plant origin with high activity and lower toxicity. Most of the chemotherapeutic agents due to their non-specific target and toxicity on active healthy cells, use is often restricted, necessitating search for newer drugs having greater potentiality.

DNA binding and apoptotic induction ability of harmalol in HepG2: Biophysical and biochemical approaches.

Harmalol administration caused remarkable reduction in proliferation of HepG2 cells with GI50 of 14.2 μM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism (CD) and differential scanning calorimetric (DSC) analysis of harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 °C.

Targeting different RNA motifs by beta carboline alkaloid, harmalol: a comparative photophysical, calorimetric, and molecular docking approach.

RNA has attracted recent attention for its key role in gene expression and targeting by small molecules for therapeutic intervention. This work focuses towards understanding interaction of harmalol, a DNA intercalator, with RNAs of different motifs viz. single-stranded A-form poly(A), double-stranded A-form of poly(C)·poly(G), and clover leaf tRNA by different spectroscopic, calorimetric, and molecular modeling techniques.

Sequence specific binding of beta carboline alkaloid harmalol with deoxyribonucleotides: binding heterogeneity, conformational, thermodynamic and cytotoxic aspects.

Background: Base dependent binding of the cytotoxic alkaloid harmalol to four synthetic polynucleotides, poly(dA).poly(dT), poly(dA-dT).poly(dA-dT), poly(dG).

Binding of alkaloid harmalol to DNA: photophysical and calorimetric approach.

Harmalol exhibits pH dependent structural equilibrium between protonated and deprotonated forms with a pKa of 7.8 as revealed from spectroscopic titration. The compound exists as protonated (structure I) and deprotonated (structure II) form in the pH range 1-7 and 9-12, respectively.

Ethanolic extract of the Goldenseal, Hydrastis canadensis, has demonstrable chemopreventive effects on HeLa cells in vitro: Drug-DNA interaction with calf thymus DNA as target.

This study tested chemotherapeutic potential of Hydrastis canadensis (HC) extract in HeLa cells in vitro, with emphasis on its drug-DNA interaction and apoptosis induction ability. Nuclear uptake of HC by DAPI, Ao/Eb staining and internucleosomal DNA damage by comet assay was studied through fluorescence microscopy. Possible changes in MMP and apoptotic signalling events were critically analyzed.

Dihydroxy-isosteviol methyl ester of Pulsatilla nigricans extract reduces arsenic-induced DNA damage in testis cells of male mice: its toxicity, drug-DNA interaction and signaling cascades.

Objective: To evaluate the ameliorative efficacy of dihydroxy-isosteviol methyl ester (DIME) of Pulsatilla nigricans extract in arsenic-induced DNA damage in testis cells of mice.

Methods: The mice were treated with sodium arsenite (SA) solution intragastrically at a dose of 20 mg/kg per day and examined at 30, 60, and 90 d after treatment. We divided SA-intoxicated mice into two sub-groups: one fed with DIME at a dose of 35 mg/kg and the other with 85% alcohol.

Poly (lactide-co-glycolide) encapsulated extract of Phytolacca decandra demonstrates better intervention against induced lung adenocarcinoma in mice and on A549 cells.

We tested relative efficacy of the extract of Phytolacca decandra (PD) and its PLGA nano-encapsulated form (NPD) in mice intoxicated with benzo[a]pyrene (BaP) (25 mg/kg b.w.) plus sodium-arsenite (SA) (10 mg/kg b.

Targeting RNA by small molecules: comparative structural and thermodynamic aspects of aristololactam-β-D-glucoside and daunomycin binding to tRNA(phe).

Background: Interaction of aristololactam-β-D-glucoside and daunomycin with tRNA(phe) was investigated using various biophysical techniques.

Methodology/principal Findings: Absorption and fluorescence studies revealed that both the compounds bind tRNA(phe) non-cooperatively. The binding of daunomycin was about one order of magnitude higher than that of aristololactam-β-D-glucoside.