Design,Synthesis, and Biological Evaluation of 2‐(2‐Bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole Derivatives as Possible Anti‐Breast Cancer Agents

Breast Cancer (BCa) is the most often diagnosed cancer among women who were in the late 1940’s. Breast cancer growth is largely dependent on the expression of estrogen and progesterone receptor. Breast cancer cells may have one, both, or none of these receptors. The treatment for breast cancer may involve surgery, hormonal therapy (Tamoxifen, an aromatase inhibitor, etc.) and oral chemotherapeutic drugs. The molecular docking technique reported the findings on the potential binding modes of the 2‐(2‐bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole derivatives with the estrogen receptor (PDB ID: 3ERT). The 1,3,4‐oxadiazole derivatives 4a – 4j have been synthesized and described by spectroscopic method. 2‐(2‐Bromo‐6‐nitrophenyl)‐5‐(4‐bromophenyl)‐1,3,4‐oxadiazole ( 4c ) was reconfirmed by single‐crystal XRD. All the compounds have been tested in combination with generic Imatinib pharmaceutical drug against breast cancer cell lines isolated from Caucasian woman MCF‐7, MDA‐MB‐453 and MCF‐10A non‐cancer cell lines. The compounds with the methoxy (in 4c ) and methyl (in 4j ) substitution were shown to have significant cytotoxicity, with 4c showing dose‐dependent activation and decreased cell viability. The mechanism of action was reported by induced apoptosis and tested by a DNA enzyme inhibitor experiment (ELISA) for Methyl Transferase. Molecular dynamics simulations were made for hit molecule 4c to study the stability and interaction of the protein?ligand complex. The toxicity properties of ADME were calculated for all the compounds. All these results provide essential information for further clinical trials.     

Multigene CRISPR/Cas9 genome editing of hybrid proline rich proteins (HyPRPs) for sustainable multi-stress tolerance in crops: the review of a promising approach

Physiology and Molecular Biology of Plants - The recent global climate change has directly impacted major biotic and abiotic stress factors affecting crop productivity worldwide. Therefore, the...     

Induced Stress on Red Blood Cell Promotes Red Blood Cell-Endothelial Adhesion

Cell and Tissue Biology - Besides disease condition, very few stress stimulants were determined to provoke red blood cell (RBC) adhesion to endothelial cells (EC). However, the possible role of...     

Correction to: Transient Sub-cellular Localization and In Vivo Protein-Protein Interaction Study of Multiple Abiotic Stress Responsive AteIF4A-III and AtALY4 Proteins in Arabidopsis thaliana

Plant Molecular Biology Reporter - The affiliation 2 in the published article was Academy of Scientific and Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam 785,006, India.     

Cholinesterase inhibitory effects of Rhizophora lamarckii,Avicennia officinalis,Sesuvium portulacastrum and Suaeda monica: Mangroves inhabiting an Indian coastal area (Vellar Estuary)

Alzheimer's disease is a progressive neurodegenerative illness accounting for approximately 50% of all types of dementia in elderly people. The only symptomatic treatment proven effective to date is the use of cholinesterase inhibitors to augment surviving cholinergic activity. The purpose of this study is to investigate cholinesterase inhibitory activity of mangroves as an alternative medicine for the treatment of Alzheimer's disease. About nine mangrove plants, which were used as folk medicine in tropical countries, were collected from Parangipettai, Vellar estuary, Tamilnadu, India. Nile Tilapia muscle homogenate was used as source of enzyme. Inhibitory effect of methanolic leaf extract was assessed under in vitro condition by incubating various concentration of the extract with total cholinesterase and butyryl cholinesterase and assessing their residual activities by Ellman's colorimetric method. The results showed that of the nine plants screened Rhizophora lamarckii, Suaeda monica, Avicennia officinalis and Sesuvium portulacastrum showed 50% inhibitory activity to both TChE and BChE at concentrations less than 2 mg/mL when compared to other plant extracts, which was comparable to the standard drug Donepezil. Phytochemical analysis showed the presence of alkaloids in high concentration which might be correlated to its cholinesterase inhibitory activity.     

High-yield production of the VP1 structural protein epitope from serotype O foot-and-mouth disease virus in Escherichia coli

For effective control of foot-and-mouth disease (FMD), the development of rapid diagnostic systems and vaccines are required against its etiological agent, FMD virus (FMDV). To accomplish this, efficient large-scale expression of the FMDV VP1 protein, with high solubility, needs to be optimized. We attempted to produce high levels of a serotype O FMDV VP1 epitope in Escherichia coli. We identified the subtype-independent serotype O FMDV VP1 epitope sequence and used it to construct a glutathione S-transferase (GST) fusion protein. For efficient production of the FMDV VP1 epitope fused to GST (VP1e–GST), four E. coli strains and three temperatures were examined. The conditions yielding the greatest level of VP1e–GST with highest solubility were achieved with E. coli BL21(DE3) at 25 °C. For high-level production, fed-batch cultures were conducted in 5-l bioreactors. When cells were induced at a high density and complex feeding solutions were supplied, approximately 11 g of VP1e–GST was obtained from a 2.9-l culture. Following purification, the VP1 epitope was used to immunize rabbits, and we confirmed that it induced an immune response.     

Density functional theory investigation of cocaine water complexes

Twenty cocaine–water complexes were studied using density functional theory (DFT) B3LYP/6-311++G** level to understand their geometries, energies, vibrational frequencies, charge transfer and topological parameters. Among the 20 complexes, 12 are neutral and eight are protonated in the cocaine-water complexes. Based on the interaction energy, the protonated complexes are more stable than the neutral complexes. In both complexes, the most stable structure involves the hydrogen bond with water at nitrogen atom in the tropane ring and C?=?O groups in methyl ester. Carbonyl groups in benzoyl and methyl ester is the most reactive site in both forms and it is responsible for the stability order. The calculated topological results show that the interactions involved in the hydrogen bond are electrostatic dominant. Natural bond orbital (NBO) analysis confirms the presence of hydrogen bond and it supports the stability order. Atoms in molecules (AIM) and NBO analysis confirms the C-H?·?·?·?O hydrogen bonds formed between the cocaine-water complexes are blue shifted in nature.     

Retraction Note to: In vitro somatic embryogenesis from immature female flower of Musa AAB cv. Chenichampa and molecular analysis of transcript factors (TFs) during somatic embryogenesis

Plant Cell, Tissue and Organ Culture (PCTOC) - This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s11240-020-01912-4     

Computational modeling of novel inhibitory peptides targeting proteoglycan like region of carbonic anhydrase IX and in vitro validation in HeLa cells

Abstract

Carbonic anhydrase IX (CAIX) is a tumour-associated, hypoxia-induced, membrane-bound metallo-enzyme which catalyzes the reversible hydration of carbon dioxide (CO₂) to bicarbonate (HCO₃^?) and proton (H⁺) ions. Over expression of CAIX is observed in cancers of colon, lung, kidney, breast, etc. CAIX plays a vital role in maintaining favourable intracellular pH for tumour cell growth and extracellular acidification which in-turn leads to drug resistance and spread of factors influencing tumour invasion. The N-terminal proteoglycan (PG) – like fragment of CAIX is unique to this isoform and is considered as potential druggable hotspot. Recently, M75 monoclonal antibody targeting the LPGEEDLPG epitope of PG like region has been proposed to reduce cellular adhesion in cancer cells. LPGEEDLPG fragment in complex with M75 has been crystallized and it serves as a strong base for development of peptide inhibitors based on interacting interfaces. Thus, in this study, an in-depth analysis of intermolecular interactions in LPGEEDLPG-M75 complex was carried out by implementing extensive molecular dynamics simulations, binding free energy calculations so as to infer the major determinant fragments of M75 that can be used as peptide inhibitors targeting PG region. Based on these analyses, 3 peptides (Pep1, Pep2 and Pep3) were synthesized and validated by in vitro assays involving cytotoxicity assessment, CAIX inhibition analysis through Direct and Indirect functional assays, and inhibition of Cell adhesion in HeLa cells. The results reveal Pep1 to be a promising inhibitor as it could efficiently modulate CAIX mediated pH homeostasis and cell adhesion in cancer cells.

Communicated by Ramaswamy H. Sarma