A5015226138- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Histone Deacetylase Inhibitors Research
- Bioactive Compounds and Antitumor Agents
- Click Chemistry and Applications
- Nanoplatforms for cancer theranostics
- Synthesis and Biological Evaluation
- Adenosine and Purinergic Signaling
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Synthesis and biological activity
- Amino Acid Enzymes and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Piperaceae Chemical and Biological Studies
- DNA Repair Mechanisms
- Protein Degradation and Inhibitors
- Immune cells in cancer
- Chemical Synthesis and Analysis
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Asymmetric Hydrogenation and Catalysis
Texas Tech University Health Sciences Center
2015-2024
Texas Tech University
2015-2024
Georgia State University
2014
USA Mitchell Cancer Institute
2013
University of South Alabama
2013
// Hanumantha Rao Madala 1 , Surendra R. Punganuru Francis Ali-Osman 2 Ruiwen Zhang 3 and Kalkunte S. Srivenugopal Department of Biomedical Sciences, School Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA Surgery the Brain Tumor Duke University, Durham, NC, Pharmacological Pharmaceutical College Houston, Correspondence to: Srivenugopal, email: Kalkunte.Srivenugopal@ttuhsc.edu Keywords: disulfiram; MGMT; glioma; chemotherapy; nanoparticles Received: September 12,...
The Near-infrared Fluorescence (NIRF) molecular imaging of cancer is known to be superior in sensitivity, deeper penetration, and low phototoxicity compared other modalities. In view an increased need for efficient targeted agents, we synthesized a NAD(P)H quinone oxidoreductase 1 (NQO1)-activatable NIR fluorescent probe (NIR-ASM) by conjugating dicyanoisophorone (ASM) fluorophore with the NQO1 substrate propionic acid (QPA). remained non-fluorescent until activation NQO1, whose expression...
Piperlongumine (PL), a small molecule alkaloid present in black pepper (Piper longum), has been reported to kill tumor cells irrespective of their p53 gene status, however, the mechanisms involved are unknown. Since is redox-sensitive protein, we hypothesized that redox imbalance induced by PL may affect structure and/or function mutant protein and promote cell death. We used two human colon cancer lines, HT29 SW620 which harbor R273H DNA contact abrogatory mutation p53. treatment...
Whether the antimutagenic DNA repair protein MGMT works solo in human cells and if it has other cellular functions is not known. Here, we show that associates with PCNA turn, cell cycle inhibitor, p21cip1 glioblastoma cancer lines. was shown to harbor a nearly perfect PCNA-Interacting Protein (PIP box) motif. Isogenic p53-null H1299 were engineered express p21 by two different procedures. Reciprocal immunoprecipitation/western blotting, Far-western confocal microscopy confirmed specific...
Human NAD(P)H quinone oxidoreductase-1 (hNQO1) is an important cancer-related biomarker, which shows significant overexpression in malignant cells. Developing effective method for detecting NQO1 activity with high sensitivity and selectivity tumors holds a great potential cancer diagnosis, treatment, management. In the present study, we report new dicyanoisophorone (DCP) based fluorescent probe (NQ-DCP) capable of monitoring hNQO1 vitro vivo both ratiometric turn-on model. NQ-DCP was...
Tumor heterogeneity and drug resistance pose severe limitations to chemotherapy of colorectal cancers (CRCs) necessitating innovative approaches trigger multiple cytocidal events for increased efficacy. Here, we developed a hybrid called KSS19 by combining the COX-2 selective NSAID rofecoxib with cis-stilbene found in combretastatin A4 (CA4), problematic, but potent antimicrotubule anti-angiogenesis agent. The structural design completely prevented isomerization CA4 its biologically inactive...
There is a desperate need for novel and efficacious chemotherapeutic strategies human brain cancers. are abundant molecular alterations along the p53 MDM2 pathways in glioma, which play critical roles drug resistance. The present study was designed to evaluate vitro vivo antitumor activity of brain-penetrating small molecule degrader, termed SP-141. In panel nine glioblastoma medulloblastoma cell lines, SP-141, as single agent, potently killed tumor-derived lines with IC50 values ranging...
Under conditions of inherent or induced mitochondrial dysfunction, cancer cells manifest overlapping metabolic phenotypes, suggesting that they may be targeted via a common approach. Here, we use multiple oxidative phosphorylation (OXPHOS)-competent and incompetent cell pairs to demonstrate treatment with α-ketoglutarate (aKG) esters elicits rapid death OXPHOS-deficient by elevating intracellular aKG concentrations, thereby sequestering nitrogen from aspartate through glutamic-oxaloacetic...
The molecular basis of anticancer and apoptotic effects R-goniothalamin (GON), a plant secondary metabolite was studied. We show that induction oxidative stress reactivation mutant p53 underlie the strong cytotoxic GON against breast cancer cells. While not toxic to MCF10a epithelial cells, SKBR3 cells harboring an R175H were highly sensitive (IC50 = 7.3 µM). Flow cytometry other pertinent assays showed GON-induced abundant reactive oxygen species (ROS), glutathione depletion, protein...
A concise stereoselective total synthesis of (+)-monocerin has been accomplished using cross metathesis, tandem dihydroxylation-S N 2 cyclisation and intramolecular alkoxycarbonylation as key steps. Cross-metathesis 2-iodo-3,4,5-trimethoxyvinylbenzene ( R)-hepten-4-ol, followed by generated a tri-substituted tetrahydrofuran ring. Finally, the dihydroisocoumarin was obtained an alkoxycarbonylation. In this paper, we have developed expedient operationally simple Pd(OAc) /bathocuproine...
The incidence of pediatric and adult brain tumors has continued to rise in the USA alkylating agent temozolomide remained sole choice chemotherapy these lethal malignancies. Therefore, there is a very urgent need design new, more effective brain‐penetrating drugs that can significantly advance survival tumor patients. We are highly interested exploiting elevated oxidative stress present gliomas have synthesized hydrophobic, non‐diuretic analog ethacrynic acid (EA) called KSS72 by removing...
In this paper a simple and efficient method for the unsymmetrical terphenyls via sequential one-pot Suzuki coupling reactions using Pd(OAc)2 without isolation of intermediate is described. The prepared were found to possess potent anticancer properties against panel cancer cells which includes A549, HeLa, MCF7, DU145, HT29 BxPC-3. Structural similarity with combretastatin A4, these disrupted tubulin polymerization in vitro destabilized microtubules cells. Flow cytometry studies indicated...
Abstract p53 gene mutations in 50% of human cancers drive the emergence oncogenic genomes and confer resistance to anticancer drugs & apoptosis. Therefore, a pharmacological reactivation mutant proteins their wild-type forms has emerged as an intense research area. We have shown that induction oxidative protein modifications primarily underlie mechanistic conversion wt or wt-like (Eur J Medchem 107:233, 2016; Int Oncol 48:1426, 2016). R248W/Q DNA contact core are highly frequent cause...
Abstract Given the molecular complexity of cancers, their extreme heterogeneity and innate or acquired resistance to anticancer drugs, there is an increasing need for hybrid drugs that can effectively simultaneously impact two more targets triggering multiple cytocidal events in synergy obtain superior chemo-sensitivities prevent tumor resistance. Therefore, we developed a drug by combining NF-kb inhibiting oxidative stress-inducing parthenolide, sesquiterpene lactone derived from plant...
Abstract Primary brain tumors and cancers metastasizing to CNS are the most challenging lethal malignancies treat. Chemotherapy with radiation has been a mainstay in their treatment, however, adverse effects such as bone marrow suppression, inefficient drug entry through BBB, intratumoral heterogeneity, overexpression of MGMT repair protein all impediments for successful treatment. Therefore, there is great need innovative exploitation targets selectively expressed effective therapy. Such an...
Abstract Goniothalamin (GTN) is a secondary metabolite styryl lactone isolated from several species of the tropical medicinal tree Goniothalamus. GTN has been shown to be cytotoxic and induce apoptosis in many cancer cell lines. This study sought define molecular basis underlying antiproliferative actions GTN. We synthesized R S enantiomers found form more against panel breast lung The IC50 lines was range 10-20 μM interestingly, SKBR3 cells, which harbor R175H mutation p53 were sensitive...