Pyrrolidine-based cationic γ-peptide: a DNA-binding molecule works as a potent anti-gene agent

Pyrrolidine-based cationic peptides showing high stability to enzyme degradation and strong binding affinity towards DNA are widely investigated as tools to interfere in gene expression. Several studies have been focused on γ-peptide analogs with modifications on the peptide backbone in the attempt to overcome solubility, uptake, and aggregation issues. Pyrrolidine-based γ-peptide derivatives having two different modes of backbone conformation show interesting properties in terms of secondary structure and affinity of binding towards nucleic acids. In this paper, we illustrate our results obtained on two cationic 8-mer γ-peptides Gp1 and Gp2, and how they differ in side-chain spacing along the backbone was tested for DNA binding and DNA transfection activity. Both γ-peptides are stable toward protease digestion. Gp1 binds to DNA more tightly than GP2. This binding ability of Gp1 is attributed to its characteristic of single-chain PPII-like conformation. The Gp1 shows a reduction in its electrophoretic mobility when treated with plasmid DNA. The DNA transfection ability of γ-peptide Gp1 was compared with commercially available transfection reagent Effectene. In each case, Gp1 significantly enhanced the transfection efficiency (40%) of plasmid in Schneider cells compared to the commercial reagent (18%). The other γ-peptide GP2 is not active

Anti-proliferative activity and characterization data on oxadiazole derivatives

10.1016/j.dib.2020.105979Data in Brief3110597

Identification of novel class of Triazolo-Thiadiazoles as potent inhibitors of human Heparanase and their anticancer activity

Expression and activity of heparanase, an endoglycosidase that cleaves heparan sulfate (HS) side chains of proteoglycans, is associated with progression and poor prognosis of many cancers which makes it an attractive drug target in cancer therapeutics

Identification of beta-aminopyrrolidine containing peptides as beta-amyloid aggregation inhibitors for Alzheimer's disease

Alzheimer's disease (AD) is caused by a series of events initiated by the production and aggregation of the amyloid beta-protein (A beta). In the early stages of the disease, A beta is released in a soluble form then progressively forms oligomeric, multimeric, and fibrillar aggregates, triggering neurodegeneration. Thus, development of inhibitors that initiate reverse A beta aggregation is thought to be a logical approach in treating AD. In this context, we developed beta-aminopyrrolidine containing 12 mer peptide 3 which is very potent in inhibiting the A beta aggregation and also reducing A beta(42)-induced cytotoxicity

Facile synthesis of 1,4-benzodiazepine-2,5-diones and quinazolinones from amino acids as anti-tubercular agents

A family of 1,4-benzodiazepine-2,5-diones and quinazolinones with diverse substituents at the C-3 position were synthesized via a novel, simple and convenient methodology using H2PtCl6 as the catalyst. The substitution at the C-3 position was varied using pre-defined amino acids as precursors. The synthesized benzodiazepines were screened for anti-mycobacterial tuberculosis (anti-TB) activity. The results revealed that the 1,4-benzodiazepine-2,5-diones displayed promising activity in comparison with their open chain precursors, which indicates that the diazepine frame is vital for their activity. The compounds 4h and 4f were found to be the lead nominees in the series with MIC values of 1.55 and 2.87 μg mL−1, respectively. A docking study was carried out on the enoyl acyl carrier protein to provide a better understanding of the mechanism of action of these compounds. Based on this study, the 1,4-benzodiazepine-2,5-dione framework is a good starting point for the development of new lead drug candidates in the treatment of multi-drug resistant tuberculosis

A trisubstituted pyrazole derivative reduces DMBA-induced mammary tumor growth in rats by inhibiting estrogen receptor-α expression

Aberrant expression of estrogen receptor alpha (ER-α) is observed in many pathological complications like breast cancer, endometrial cancer, and in osteoporosis. ER-α plays a vital role in the initiation and progression of breast cancer and confers chemo and radioresistance to the cancer cells by upregulating expression of anti-apoptotic proteins. The synthetic pyrazole derivative 3-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl)pyridine (compound 5d) displays significant cytotoxicity against mammary carcinoma cells. Molecular docking studies revealed that compound 5d binds to ligand binding domain of (ER-α). In vivo studies were carried out to investigate ER-α expression by immunohistochemistry and quantitative RT-PCR, which revealed reduction of ER-α in tumor cells upon treatment with compound 5d indicating its ER-α antagonistic effect. Our study ascertains compound 5d as a potent inhibitor of mammary carcinoma cells

Multi-pharmacophore Approach to Bio-therapeutics: Piperazine Bridged Pseudo-peptidic Urea/Thiourea Derivatives as Anti-oxidant Agents

In an attempt to develop synergetic, potential and selective anti-oxidant agents, a series of novel piperazine bridged pseudo-peptidic urea/thiourea derivatives (5a-x) are designed by molecular docking study, synthesized and evaluated for their in-vitro anti-oxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and dimethyl-4-phenylenediamine (DMPD) methods. The results revealed that compounds 5q, 5s, 5w and 5x are good anti-oxidant agents. Amongst, compounds with aromatic side chain, thioureal fragment with electron donating group-substitution, particularly, 5s and 5w are the most active members exhibiting remarkable anti-oxidant property. The docking results are complementary to the experimental results. The correlation study revealed that compounds derived from phenylalanine and tryptophan containing electron donating group are excellent antioxidants. GRAPHICS]

Identification of novel benzimidazole-based small molecule targeting dual targets Tankyrase and Bcl2 to induce apoptosis in Colon cancer

Tankyrase is a crucial protein involved in the regulation of various proteins, among which the Wnt / beta catenin pathway and TERF1 are the main critical pathway proteins. Deregulation of the Wnt / beta catenin pathway has been reported in various cancers. Tankyrase regulates the Wnt / beta catenin pathway by stabilizing AXIN1 and AXIN2 through a proteasomal degradation pathway. Targeting tankyrase is an attractive strategy to target cancer due to the importance of tankyrase in the regulation of TERF1, which is directly involved in the maintenance of telomeric length. Bcl2, another crucial antiapoptotic protein predominantly overexpressed in various cancer types involves cell survival and chemo-resistance. Synthesized compounds have displayed potent antiproliferative activity against various cancer cells specifically HCT116 cells displayed the most sensitivity to compounds with IC50 of 32.9 mu M. The compound induces efficient apoptosis which was unveiled by Annexin V / PI double staining in HCT116 cells. Colony formation capabilities were diminished in the compound treatment group which displays the potent antiproliferative activity of the compound against HCT116 cells. In silico studies displayed strong interaction of compound 5d with Tankyrase and Bc12 with a strong binding score of -6.70 kcal/mol and -6.16 kcal/mol respectively. (C) 2022 Elsevier B.V. All rights reserved