Publications by authors named "Manu Lopus"

It is crucial to comprehend protein misfolding and aggregation in the domains of biomedicine, pharmaceuticals, and proteins. Amyloid fibrils are formed when proteins misfold and assemble, resulting in the debilitating illness known as "amyloidosis". This work investigates lysozyme fibrillation with pluronics (F68 and F127).

View Article and Find Full Text PDF

We report the identification of an interesting mode of action by sorafenib (SF) (Nexavar) in triple-negative breast adenocarcinoma MDA-MB-231 cells. The dying cells presented features of apoptosis, such as externalization of phosphatidylserine and cleaved caspase-3, and autophagy-mediated cell death, such as formation of autophagosomes and autolysosomes, the overexpression of LC3-II, and the presence of LAMP1-positive vacuoles, while displaying insufficient autophagic flux. Components of endoplasmic reticulum stress (ER stress; PERK and CHOP) and of necroptosis (p-MLKL) were also elevated considerably.

View Article and Find Full Text PDF

Fabrication of gold nanoparticles (GNPs) with phytochemicals is an emerging green nanotechnology approach with therapeutic implications. Garlic, known for its culinary and medicinal properties, has been extensively investigated for its anticancer properties. Here, we report a method to substantially enhance the antiproliferative potency of garlic by functionalizing its phytochemicals to GNPs and demonstrate a possible mechanism of action of these nanoparticles in the triple-negative breast cancer cell line, MDA-MB-231.

View Article and Find Full Text PDF

Collective functionalization of the phytochemicals of medicinal herbs on nanoparticles is emerging as a potential cancer therapeutic strategy. This study presents the facile synthesis of surface-functionalized gold nanoparticles using (Brahmi; ) phytochemicals and their therapeutically relevant mechanism of action in the colorectal cancer cell line, HT29. The nanoparticles were characterized using UV-visible spectroscopy, TEM-EDAX, zeta potential analysis, TGA, FTIR and H NMR spectroscopy, and HR-LC-MS.

View Article and Find Full Text PDF

Erastin (ERN) is a small molecule that induces different forms of cell death. For example, it has been reported to induce ferroptosis by disrupting tubulin subunits that maintain the voltage-dependent anion channels (VDACs) of mitochondria. Although its possible binding to tubulin has been suggested, the fine details of the interaction between ERN and tubulin are poorly understood.

View Article and Find Full Text PDF

Respiratory tract infections (RTIs) are a common cause of mortality and morbidity in the human population. The overuse of antibiotics to overcome such infections has led to antibiotic resistance. The emergence of multidrug resistant bacteria is necessitating the development of novel therapeutic techniques in order to avoid a major global clinical threat.

View Article and Find Full Text PDF

Carbon nanotubes (CNTs) are allotropes of carbon, composed of carbon atoms forming a tube-like structure. Their high surface area, chemical stability, and rich electronic polyaromatic structure facilitate their drug-carrying capacity. Therefore, CNTs have been intensively explored for several biomedical applications, including as a potential treatment option for cancer.

View Article and Find Full Text PDF

Cathepsin B is a lysosomal cysteine protease, contributing to vital cellular homeostatic processes including protein turnover, macroautophagy of damaged organelles, antigen presentation, and in the extracellular space, it takes part in tissue remodeling, prohormone processing, and activation. However, aberrant overexpression of cathepsin B and its enzymatic activity is associated with different pathological conditions, including cancer. Cathepsin B overexpression in tumor tissues makes this enzyme an important target for smart delivery systems, responsive to the activity of this enzyme.

View Article and Find Full Text PDF

Nano-ayurvedic medicine is an emerging field in which nanoparticles are functionalized with active principles of potent ayurvedic herbs to enhance their efficacy and target-specific delivery. Scientific advances in the past couple of decades have revealed the molecular mechanisms behind the anticancer potential of several ayurvedic herbs, attributed chiefly to their secondary metabolites including polyphenols and other active substances. With the advancement of nanotechnology, it has been established that size-, shape-, and surface-chemistry-optimized nanoparticles can be utilized as synergizing carriers for these phytochemicals.

View Article and Find Full Text PDF

Several microbial pathogens are capable of forming biofilms. These microbial communities pose a serious challenge to the healthcare sector as they are quite difficult to combat. Given the challenges associated with the antibiotic-based management of biofilms, the research focus has now been shifted towards finding alternate treatment strategies that can replace or complement the antibacterial properties of antibiotics.

View Article and Find Full Text PDF

Shikonin (SK), a naphthoquinone compound from the purple gromwell, Lithospermum erythrorhizon, possesses a considerable antiproliferative potential. By using a combination of biophysical techniques, cellular assays, immunofluorescence imaging, and molecular dynamic simulation, we identified a possible mechanism of action of SK. SK inhibited the viability of the triple negative breast cancer cells MDA-MB-231 (IC of 1 ± 0.

View Article and Find Full Text PDF

Vesicular systems such as niosomes provide an alternative to improve drug delivery systems. The efficiency of a drug delivery vehicle is strongly dependent on its components which decide its interaction with partitioned drug(s) and locus of site of partitioning. A quantitative understanding of the physical chemistry underlying partitioning of drugs in complex systems of self-assemblies such as niosomes is scarcely available.

View Article and Find Full Text PDF

Silver nanoparticles, shaped and stabilized by various means, are known to alter biological systems and promote cytotoxicity. However, the precise mechanism by which they induce toxic outcomes in cancer cells is poorly understood. Using a combination of cellular and biophysical assays and proteomic and metabolomic analyses, we report the cytotoxic mechanism of action of tryptone-stabilized silver nanoparticles (T-AgNPs).

View Article and Find Full Text PDF

Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) are proteins and protein segments that usually do not acquire well-defined folded structures even under physiological conditions. They are abundantly present and challenge the "one sequence-one structure-one function" theory due to a lack of stable secondary and/or tertiary structure. Due to conformational flexibility, IDPs/IDPRs can bind with multiple interacting partners with high-specificity and low-affinity and perform essential biological functions associated with signalling, recognition and regulation.

View Article and Find Full Text PDF

Many diseases heal spontaneously. The common cold, for example, remedies itself within a few days in people with an uncompromised immune system. If a disease with a poor prognosis heals in the absence of a targeted therapeutic, many even call it a miracle cure.

View Article and Find Full Text PDF

Aim: Elucidation of the antiproliferative efficacy and mechanism of action of a design-optimized noscapine analog, N-4-CN.

Methods: Cell viability was studied using an MTT assay. The drug-tubulin interactions were investigated using spectrofluorometry.

View Article and Find Full Text PDF

Objectives: To examine the antiproliferative effect of a rationally designed, novel noscapine analogue, 9-((perfluorophenyl)methylene) aminonoscapine, '9-PAN') on MDA-MB-231 breast cancer cell line, and to elucidate the underlying mechanism of action.

Methods: The rationally designed Schiff base-containing compound, 9-PAN, was characterized using IR, NMR and mass spectra analysis. The effect of the compound on cell viability was studied using an MTT assay.

View Article and Find Full Text PDF

Aim: To rationally-design, synthesize, characterize, biologically evaluate, and to elucidate the anticancer mechanism of action of a novel analogue of noscapine, N-propargyl noscapine (NPN), as a potential drug candidate against triple-negative breast cancer (TNBC).

Materials And Methods: After the synthesis and IR, H, C NMR and mass spectral characterization of NPN, its antiproliferative efficacy against different cancer cell lines was investigated using Sulforhodamine B assay. Cell cycle progression was analysed using flow cytometry.

View Article and Find Full Text PDF

Gold nanoparticles of different sizes, shapes, and decorations exert a variety of effects on biological systems. We report a novel mechanism of action of chemically modified, tryptone-stabilized gold nanoparticles (T-GNPs) in the triple-negative breast cancer (TNBC) cell line, MDA-MB-231. The T-GNPs, synthesized using HAuCl.

View Article and Find Full Text PDF

Like the organism they constitute, the cells also die in different ways. The death can be predetermined, programmed, and cleanly executed, as in the case of apoptosis, or it can be traumatic, inflammatory, and sudden as many types of necrosis exemplify. Nevertheless, there are a number of cell deaths-some of them bearing a resemblance to apoptosis and/or necrosis, and many, distinct from each-that serve a multitude of roles in either supporting or disrupting the homoeostasis.

View Article and Find Full Text PDF

Gold nanoparticles (GNPs) of different sizes and shapes have been investigated extensively for their therapeutic potential against several diseases including cancer. However, the mechanisms with which they affect the cells are yet to be fully comprehended. In this study, we report the strong antiproliferative potential of novel, star-shaped ("stellate") GNPs that target tubulin-the building-block protein of the cytoskeletal filaments called microtubules-and disrupt microtubule network integrity.

View Article and Find Full Text PDF

Background: Noscapine is a non-narcotic, antitussive alkaloid isolated from plants of Papaveraceae family. This benzylisoquinoline alkaloid and its synthetic derivatives, called noscapinoids, are being evaluated for their anticancer potential.

Methods: The structure of a novel analogue, N-(3-bromobenzyl) noscapine (N-BBN) was elucidated by X-ray crystallography.

View Article and Find Full Text PDF

Triphala (Trl) is an ayurvedic formulation used for treating disorders of the digestive, respiratory, and nervous systems. Its anticancer properties have also been documented. We studied effects of Trl on tubulin, a target protein for several anticancer drugs, and systematically elucidated a possible antiproliferative mechanism of action of Trl.

View Article and Find Full Text PDF

Saffron, a spice from Crocus sativus, has been known for its health benefits and medicinal properties. Safranal is a component of saffron and is known for its antioxidant and anticancer properties. In this study, we elucidated a possible tubulin-targeted antiproliferative mechanism of action of safranal.

View Article and Find Full Text PDF