Staphylococcus aureus major cell division protein FtsZ assembly is inhibited by silibinin, a natural flavonolignan that also blocked bacterial growth and biofilm formation.

The bacterial cell division protein FtsZ has been considered a potential therapeutic target due to its rapid treadmilling that induces cellular wall construction in bacteria. The current study discovered a novel antimicrobial compound, silibinin, a natural flavonolignan and its impact on the recombinant S. aureus FtsZ (SaFtsZ).

The interplay between autophagy and apoptosis: its implication in lung cancer and therapeutics.

Maintaining cellular homeostasis relies on the interplay between apoptosis and autophagy, and disruption in either of these processes can contribute to the development of cancer. Autophagy can hinder the apoptotic process, and when autophagy is inhibited in such instances, it can enhance the rate of apoptosis. However, evidence suggests that excessive autophagy can also lead to apoptotic cell death.

Heavy water (DO) induces autophagy-dependent apoptotic cell death in non-small cell lung cancer A549 cells by generating reactive oxygen species (ROS) upon microtubule disruption.

Objective: Deuterium oxide (DO) or heavy water is known to have diverse biological activities and have a few therapeutic applications due to its limited toxicity to human subjects. In the present study, we investigated the mechanism of DO-induced cytotoxicity in non-small cell lung cancer A549 cells.

Results: We found that DO-treatment resulted in cytotoxicity, cell cycle arrest, and apoptosis in A549 cells in a dose-dependent fashion.

Current Therapeutic Strategies and Possible Effective Drug Delivery Strategies against COVID-19.

COVID-19 pandemic is the biggest global crisis. The frequent mutations in coronavirus to generate new mutants are of major concern. The pathophysiology of SARS-CoV-2 infection has been well studied to find suitable molecular targets and candidate drugs for effective treatment.

Computational prediction of the molecular mechanism of statin group of drugs against SARS-CoV-2 pathogenesis.

Recently published clinical data from COVID-19 patients indicated that statin therapy is associated with a better clinical outcome and a significant reduction in the risk of mortality. In this study by computational analysis, we have aimed to predict the possible mechanism of the statin group of drugs by which they can inhibit SARS-CoV-2 pathogenesis. Blind docking of the critical structural and functional proteins of SARS-CoV-2 like RNA-dependent RNA polymerase, M-protease of 3-CL-Pro, Helicase, and the Spike proteins ( wild type and mutants from different VOCs) were performed using the Schrodinger docking tool.

Natural flavonoid morin showed anti-bacterial activity against Vibrio cholera after binding with cell division protein FtsA near ATP binding site.

Background: Increasing antibiotic-resistance in bacterial strains has boosted the need to find new targets for drug delivery. FtsA, a major bacterial divisome protein can be a potent novel drug-target.

Methods And Results: This study finds, morin (3,5,7,2',4'-pentahydroxyflavone), a bio-available flavonoid, had anti-bacterial activities against Vibrio cholerae, IC (50 μM) and MIC (150 μM).

NMK-BH2, a novel microtubule-depolymerising bis (indolyl)-hydrazide-hydrazone, induces apoptotic and autophagic cell death in cervical cancer cells by binding to tubulin at colchicine - site.

Background: Microtubules, the key components of the eukaryotic cytoskeleton and mitotic spindle, are one of the most sought-after targets for cancer chemotherapy, especially due to their indispensible role in mitosis. Cervical cancer is a prevalent malignancy among women of developing countries including India. In spite of the remarkable therapeutic advancement, the non-specificity of chemotherapeutic drugs adversely affect the patients' survival and well-being, thus, necessitating the quest for novel indole-based anti-microtubule agent against cervical cancer, with high degree of potency and selectivity.

Targeting cellular microtubule by phytochemical apocynin exhibits autophagy-mediated apoptosis to inhibit lung carcinoma progression and tumorigenesis.

Background: Lung cancer is the leading cause of cancer-related deaths worldwide. Several targets have been identified for lung cancer therapy, amongst which 'Microtubule' and its dynamics are the most widely studied and used in therapy. Tubulin-microtubule polymer dynamics are highly sought after targets in the field of anti-cancer drug designing.

FtsA-FtsZ interaction in Vibrio cholerae causes conformational change of FtsA resulting in inhibition of ATP hydrolysis and polymerization.

Proper interaction between the divisome proteins FtsA and FtsZ is important for the bacterial cell division which is not well characterized till date. In this study, the objective was to understand the mechanism of FtsA-FtsZ interaction using full-length recombinant proteins. We cloned, over-expressed, purified and subsequently characterized FtsA of Vibrio cholerae (VcFtsA).

Enhanced antifungal activity of fluconazole conjugated with Cu-Ag-ZnO nanocomposite.

Cu-Ag-ZnO nanocomposite (NC) has been successfully synthesized by mechanical alloying the Cu, Zn and Ag powder mixture under Ar atmosphere within 4 h of milling. The nanocomposite is then conjugated with the antifungal drug fluconazole by adding 5 wt% powdered drug to the NC and mechanical alloying the total powder mixture for one more hour. The Rietveld refinement of XRD data and FTIR spectrum analyses reveal the detailed structural and microstructural characterizations of the nanocomposite-drug conjugate (NC-DC).

Paclitaxel-encapsulated core-shell nanoparticle of cetyl alcohol for active targeted delivery through oral route.

Paclitaxel (PTX) has no clinically available oral formulations. Cetyl alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase that are overexpressed in cancer cells. So, PTX-encapsulated core-shell nanoparticle of cetyl alcohol (PaxSLN) could target the cancer cells through oral route.

Correction to: Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway.

The original version of this article unfortunately contained an error in acknowledgment text. The authors would like to include a statement: "Moumita Dasgupta is supported by Junior Research Fellowship from University Grant Commission, India." in acknowledgment section.

A novel triazole, NMK-T-057, induces autophagic cell death in breast cancer cells by inhibiting γ-secretase-mediated activation of Notch signaling.

Notch signaling is reported to be deregulated in several malignancies, including breast, and the enzyme γ-secretase plays an important role in the activation and nuclear translocation of Notch intracellular domain (NICD). Hence, pharmacological inhibition of γ-secretase might lead to the subsequent inhibition of Notch signaling in cancer cells. In search of novel γ-secretase inhibitors (GSIs), we screened a series of triazole-based compounds for their potential to bind γ-secretase and observed that 3-(3'4',5'-trimethoxyphenyl)-5-(-methyl-3'-indolyl)-1,2,4-triazole compound (also known as NMK-T-057) can bind to γ-secretase complex.

Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway.

Paclitaxel is one of the most commonly used drugs for the treatment of nonsmall cell lung cancer (NSCLC). However acquired resistance to paclitaxel, epithelial to mesenchymal transition and cancer stem cell formation are the major obstacles for successful chemotherapy with this drug. Some of the major reasons behind chemoresistance development include increased ability of the cancer cells to survive under stress conditions by autophagy, increased expression of drug efflux pumps, tubulin mutations etc.

Metformin exhibited anticancer activity by lowering cellular cholesterol content in breast cancer cells.

Metformin, a widely prescribed anti-diabetic drug, shows anticancer activity in various cancer types. Few studies documented that there was a decreased level of LDL and total cholesterol in blood serum of metformin users. Based on these views, this study aimed to determine if metformin exhibits anticancer activity by alleviating cholesterol level in cancer cells.

Theaflavin and epigallocatechin-3-gallate synergistically induce apoptosis through inhibition of PI3K/Akt signaling upon depolymerizing microtubules in HeLa cells.

Theaflavin (TF) and epigallocatechin-3-gallate (EGCG) both have been reported previously as microtubule depolymerizing agents that also have anticancer effects on various cancer cell lines and in animal models. Here, we have applied TF and EGCG in combination on HeLa cells to investigate if they can potentiate each other to improve their anticancer effect in lower doses and the underlying mechanism. We found that TF and EGCG acted synergistically, in lower doses, to inhibit the growth of HeLa cells.

Design, synthesis and biological evaluation of a novel library of antimitotic C-aroyl/arylimino tryptamine derivatives that are also potent inhibitors of indoleamine-2, 3-dioxygenase (IDO).

A novel library of C-substituted tryptamines (based on diverse C-aroyl/arylimino indoles and indole-diketopiperazine hybrids) possessing antimitotic properties were designed, synthesized and screened for their inhibitory activity against tubulin polymerization, and against proliferation of A549 lung cancer, HeLa cervical cancer, MCF7 breast cancer and HePG2 liver cancer cell lines. The design of molecules were inspired from known antimitotic compounds and natural products. The molecular docking of the designed compounds indicated that they bind to the colchicin binding site of tubulin.

Unveiling the Potential of Unfused Bichromophoric Naphthalimide To Induce Cytotoxicity by Binding to Tubulin: Breaks Monotony of Naphthalimides as Conventional Intercalators.

In the development of small-molecule drug candidates, naphthalimide-based compounds hold a very important position as potent anticancer agents with considerable safety in drug discoveries. Being synthetically and readily accessible, naphthalimide compounds with planar architecture have been developed mostly as DNA-targeting intercalators. However, in this article, it is demonstrated, for the first time, that an unfused naphthalimide-benzothiazole bichromophoric compound 2-(6-chlorobenzo[ d] thiazol-2-yl)-1 H-benzo[ de] isoquinoline-1,3(2 H)-dione (CBIQD), seems to expand the bioactivity of naphthalimide as anti-mitotic agent also.

Paclitaxel resistance development is associated with biphasic changes in reactive oxygen species, mitochondrial membrane potential and autophagy with elevated energy production capacity in lung cancer cells: A chronological study.

Paclitaxel (Tx) is one of the first-line chemotherapeutic drugs used against lung cancer, but acquired resistance to this drug is a major challenge against successful chemotherapy. In this work, we have focused on the chronological changes of various cellular parameters and associated effect on Tx (10 nM) resistance development in A549 cell line. It was observed, at initial stage, the cell death percentage due to drug treatment had increased up to 20 days, and thereafter, it started declining and became completely resistant by 40 days.

Azadiradione ameliorates polyglutamine expansion disease in Drosophila by potentiating DNA binding activity of heat shock factor 1.

Aggregation of proteins with the expansion of polyglutamine tracts in the brain underlies progressive genetic neurodegenerative diseases (NDs) like Huntington's disease and spinocerebellar ataxias (SCA). An insensitive cellular proteotoxic stress response to non-native protein oligomers is common in such conditions. Indeed, upregulation of heat shock factor 1 (HSF1) function and its target protein chaperone expression has shown promising results in animal models of NDs.

A Facile and Microwave-assisted Rapid Synthesis of 2-Arylamino-4-(3'-indolyl)- thiazoles as Apoptosis Inducing Cytotoxic Agents.

Background And Objective: The clinical success of the chemotherapeutic drugs is restricted by the nonspecific toxicity-related adverse side effects. The diverse implication of indoles and thiazoles in medicinal chemistry prompted us to develop a new series of novel 2-aryl-amino-4-(3'-indolyl)thiazoles as more effective and less toxic anti-cancer compounds.

Method And Results: One-pot microwave-assisted rapid and high yielding synthesis of 2-arylamino-4-(3'- indolyl)thiazoles involved the reaction of easily available α-tosyloxy-ketones with N-arylthioureas in polyethylene glycol-400 (PEG-400).

Development of Novel Bis(indolyl)-hydrazide-Hydrazone Derivatives as Potent Microtubule-Targeting Cytotoxic Agents against A549 Lung Cancer Cells.

The biological significance of microtubules makes them a validated target of cancer therapy. In this study, we have utilized indole, an important pharmacological scaffold, to synthesize novel bis(indolyl)-hydrazide-hydrazone derivatives (NMK-BH compounds) and recognized NMK-BH3 as the most effective one in inhibiting A549 cell proliferation and assembly of tissue-purified tubulin. Cell viability experiments showed that NMK-BH3 inhibited proliferation of human lung adenocarcinoma (A549) cells, normal human lung fibroblasts (WI38) and peripheral blood mononuclear cells (PBMC) with IC50 values of ∼2, 48.