Nitesh Kumar Nandwana

The Wistar Institute

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Anil Kumar

Birla Institute of Technology and Science, Pilani

Shiv Dhiman

University of Manitoba

Hitesh Kumar Saini

Chennai Mathematical Institute

Krishnan Rangan

Birla Institute of Technology and Science, Pilani

Vikki N. Shinde

Birla Institute of Technology and Science, Pilani

Bhaskar C. Das

Icahn School of Medicine at Mount Sinai

Om Prakash Patel

Mahindra Group (India)

Dalip Kumar

Birla Institute of Technology and Science, Pilani

Sonam Jaspal

Birla Institute of Technology and Science, Pilani

Anil Kumar

Shiv Nadar University

Cooperative Institutions

Birla Institute of Technology and Science, Pilani

University of California, Irvine

Institut Teknologi dan Sains Mandala

The Wistar Institute

Poultry Research Institute

Long Island University

University of Nebraska Medical Center

UC Irvine Health

University of Nebraska at Omaha

Nipissing University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

STEM-28. THE ROLE OF LONP1 IN DRIVING ENHANCED PMT IN THE 'LEADING EDGE' NICHE IN GLIOBLASTOMA

Neuro-Oncology (2022)

José Antonio Lepe Chris Douglas Kaijun Di Nitesh Kumar Nandwana Bhaskar C. Das

Abstract Glioblastoma (GBM), a high grade brain tumor, possesses poor overall survival with less than 5% surviving past five years. Previously, the TCGA classifications for GBM have included the mesenchymal, proneural, classical and neural subtypes with their own respective expression profiles and survival. Recent omics analysis has revealed other key aspects of GBM pathology, including intratumoral heterogeneity spanning all subtypes and enhanced stemness and treatment resistance and other hallmarks of proneural mesenchymal transition (PMT) following treatment with first-line standard of care treatment with radiation therapy and temozolomide (TMZ). Invading glioma stem cells (GSC) with high Nestin and hypoxia-inducible factor 1 alpha (HIF-1α) expression have been theorized to contribute to recurrence. HIF-1α acts as a master regulator driving increased stemness, invasiveness and angiogenesis. Interestingly, HIF-1α and nuclear respiratory factor-2 both upregulate Lon peptidase 1 (LonP1) in response to increased hypoxia or reactive oxygen species (ROS) production. LonP1 has been shown to drive increased metastasis, tumor growth and epithelial-mesenchymal transition (EMT), an analog of PMT, in colon cancer, melanoma and other cancer types. In a recently elucidated GBM organoid model, we present new findings demonstrating the importance of LonP1 in driving enhanced, transient PMT near the ‘invading edge’. This includes the enhanced expression of several key drivers of PMT and phenotypic hallmarks, such as increased invasiveness, proliferation and poorer survival.

Temozolomide

Nestin

BMI1

10.1093/neuonc/noac209.145

Cite

Citations (0)

CCDC 1562241: Experimental Crystal Structure Determination

The Cambridge Structural Database (2020)

Hitesh Kumar Saini Nitesh Kumar Nandwana Shiv Dhiman Krishnan Rangan Anil Kumar Anal

10.5517/ccdc.csd.cc1pfmwm

Cite

Citations (0)

EXTH-19. EVALUATING THE ANTI-TUMOR EFFECT OF A NOVEL THERAPEUTIC AGENT, MAGMAS INHIBITOR, IN MALIGNANT GLIOMA

Neuro-Oncology (2020)

Kaijun Di Senjie Du José Antonio Lepe Nitesh Kumar Nandwana Bhaskar C. Das

Abstract BACKGROUNDS Glioblastoma (GBM) is an aggressive infiltrative brain tumor, and has an extremely poor prognosis despite the use of multiple treatment modalities, including surgery, radiation, and chemotherapy. Meanwhile, mitochondrial changes represent a significant part of cancer cell biology since cancer cells must survive and adapt to challenging microenvironments, specifically in conditions where tumor growth makes oxygen and glucose scarce. As GBM is characterized by extensive hypoxia-induced phenotypic changes such as abnormal vascular proliferation and necrosis, regulation of mitochondrial function could be a novel approach for treating GBM that currently lacks effective therapies. Magmas (mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction) is a nuclear gene that encodes for the mitochondrial import inner membrane translocase subunit Tim16. We previously demonstrated that a novel Magmas inhibitor, BT#9, significantly exerted anti-tumor effect in glioma in vitro, and may cross the blood brain barrier in vivo, indicating that Magmas inhibitor may be a new chemotherapeutic agent for the treatment of GBM. METHODS In this study, the antitumor effect of Magmas inhibitor BT#9 was tested in an orthotopic xenograft model of human GBM. The molecular mechanism of BT#9 was investigated using glioma cell lines. RESULTS The mice were tolerated to BT#9, and there was no statistical difference in the weight of animals between the control and MTD (Maximum-tolerated Dose, 50mg/kg) groups. The immunocompromised mice, intracranially implanted with human D-54 GBM xenografts, survived significantly longer than the controls (P< 0.5) when treated with BT#9 at MTD. In vitro study showed that the MAP kinase pathways are involved in BT#9-induced tumor suppression. DISCUSSION This is the first study on the role of Magmas in glioma in vivo. Our findings suggested that Magmas plays a key role in glioma survival and targeting Magmas by Magmas inhibitor has the potential to become a therapeutic strategy in glioma patients.

10.1093/neuonc/noaa215.373

Cite

Citations (1)

Discovery and Validation of Novel LonP1 and Proteasome Inhibitor in IDH1-R132H Malignant Astrocytoma Models

SSRN Electronic Journal (2023)

Chris Douglas Naomi Lomeli Javier Lepe Kaijun Di Nitesh Kumar Nandwana

Malignant astrocytomas are aggressive glial tumors that have poor prognosis and limited treatments available following recurrence. These tumors are characterized by extensive hypoxia-induced, mitochondria-dependent changes such as glycolytic respiration, increased chymotrypsin-like (CT-L) proteasome activity, decreased apoptosis, and increased invasiveness. Mitochondrial Lon Peptidase 1 (LonP1) is an ATP-stimulated protease directly upregulated by hypoxia-inducible factor 1 alpha (HIF-1α). Both LonP1 expression and CT-L proteasome activities are increased in human astrocytomas and are associated with a high tumor grade and poor patient survival. Dual LonP1 and CT-L inhibition exhibits synergy against multiple myeloma cancer lines; however, no similar findings are reported in other cancers. We now report that dual LonP1 and CT-L inhibition has synergistic toxicity in malignant glioma models, and especially in IDH mutant grade IV astrocytoma when compared to IDH wildtype grade IV astrocytoma (glioblastoma, GBM), due to increased reactive oxygen species (ROS) generation and autophagy. A novel small molecule, BT317, was derived from the previously published coumarinic compound 4 (CC4) using structure-activity modeling and was found to inhibit both LonP1 and CT-L proteasome activity and subsequently induce ROS accumulation and autophagy-dependent cell death in high-grade IDH1 mutated astrocytoma lines. In vitro, BT317 also had enhanced synergy with the commonly used chemotherapeutic temozolomide (TMZ), which blocked BT317-induced autophagy. This novel dual inhibitor also displayed selective activity in the tumor microenvironment and demonstrated therapeutic efficacy both as a single agent and in combination TMZ in IDH mutant astrocytoma patient-derived xenograft models. In conclusion, we show that BT317, a dual LonP1, and CT-L proteasome inhibitor exhibited promising anti-tumor activity and could be a promising candidate for clinical translation in the space of IDH mutant malignant astrocytoma therapeutics.

10.2139/ssrn.4354055

Cite

Citations (2)

Vanadyl Acetylacetonate Catalyzed Methylenation of Imidazo[1,2‐a]pyridines by Using Dimethylacetamide as a Methylene Source: Direct Access to Bis(imidazo[1,2‐a]pyridin‐3‐yl)methanes

Advanced Synthesis & Catalysis (2016)

Pinku Kaswan Nitesh Kumar Nandwana Brenton DeBoef Anil Kumar

Abstract An efficient protocol has been developed for the methylenation of imidazo[1,2‐ a ]pyridines using dimethylacetamide (DMA) as methylene source in the presence of vanadyl acetylacetonate [VO(acac) 2 ] as the catalyst and iodobenzene diacetate as the oxidant. The reaction involves coupling of sp 3 ‐ and sp 2 ‐hybridized carbons and proceeds through the formation of an iminium ion. A wide variety of imidazo[1,2‐ a ]pyridines were converted to bis(imidazo[1,2‐ a ]pyridin‐3‐yl)methanes in good to excellent yields. A gram‐scale reaction demonstrated the potential for the scale‐up processes. magnified image

Methylene

Iodobenzene

Dimethylacetamide

Iminium

10.1002/adsc.201600225

Cite

Citations (51)

Synthesis of π‐Expanded Azole‐Fused Imidazo[1,2‐a]pyridine Derivatives and their Photophysical Properties

European Journal of Organic Chemistry (2020)

Nitesh Kumar Nandwana Shiv Dhiman Vikki N. Shinde Uwe Beifuß Anil Kumar

A Highly efficient copper‐catalyzed one‐pot sequential approach has been developed for the synthesis of azole‐fused imidazo[1,2‐ a ]pyridines with 2‐(2‐bromophenyl)imidazo[1,2‐ a ]pyridine‐3‐carbaldehydes as substrates. The one‐pot approach involved a sequential imidazole/benzimidazole formation followed by a copper‐catalyzed intramolecular Ullmann type C–N coupling. The method tolerated a variety of functional groups and offered the desired products in good to excellent (50–85 %) yields. The photophysical properties of the compounds synthesized were evaluated by UV/Vis and fluorescence spectroscopy in CH 3 CN. The π‐expanded azole‐fused imidazo[1,2‐ a ]pyridines displayed high fluorescence emission with large Stokes shifts and moderate to good quantum yields. A pronounced positive solvatochromism and aggregation caused quenching (ACQ) was observed for 2,3‐bis(4‐methoxyphenyl)‐12‐methylimidazo[1,2‐a]pyrido[2',1':2,3]imidazo[4,5‐c]quinoline.

Benzimidazole

Quinoline

Azole

Imidazole

Solvatochromism

10.1002/ejoc.202000236

Cite

Citations (17)

Copper and palladium-catalyzed sequential reactions: one-pot synthesis of isoindolo[2,1-b]isoquinolin-7(5H)-ones

Organic & Biomolecular Chemistry (2019)

Hitesh Kumar Saini Shiv Dhiman Nitesh Kumar Nandwana Krishnan Rangan Anil Kumar

A highly efficient protocol has been developed for the synthesis of diversely substituted isoindolo[2,1-b]isoquinolin-7(5H)-ones through sequential Cu(ii)-catalyzed Sonogashira coupling, intramolecular hydroamidation followed by palladium-catalyzed ligand free Heck reaction.

10.1039/c9ob00440h

Cite

Citations (10)

Recent Advances in Metal-Catalyzed Approaches for the Synthesis of Quinazoline Derivatives

Molecules (2024)

Nitesh Kumar Nandwana Om Prakash Patel Manish Kumar Mehra Anil Kumar Joseph M. Salvino

Quinazolines are an important class of heterocyclic compounds that have proven their significance, especially in the field of organic synthesis and medicinal chemistry because of their wide range of biological and pharmacological properties. Thus, numerous synthetic methods have been developed for the synthesis of quinazolines and their derivatives. This review article briefly outlines the new synthetic methods for compounds containing the quinazoline scaffold employing transition metal-catalyzed reactions.

Quinazoline

Organic Synthesis

10.3390/molecules29102353

Cite

Citations (2)

ChemInform Abstract: Synthesis of Aza‐Fused Isoquinolines Through Domino Cross‐Aldol Condensation and Palladium‐Catalyzed Intramolecular Direct Arylation.

ChemInform (2015)

Shiv Dhiman Kasiviswanadharaju Pericherla Nitesh Kumar Nandwana Dalip Kumar Anil Kumar

Abstract The reaction fails using 2‐chlorobenzaldehyde instead of 2‐bromobenzaldehyde.

Domino

Aldol condensation

Aldol reaction

10.1002/chin.201507234

Cite

Citations (0)

Design and Synthesis of Imidazo/Benzimidazo[1,2-c]quinazoline Derivatives and Evaluation of Their Antimicrobial Activity

ACS Omega (2018)

Nitesh Kumar Nandwana Rajnish Prakash Singh Om Prakash Patel Shiv Dhiman Hitesh Kumar Saini

A new class of fused quinazolines has been designed and synthesized via copper-catalyzed Ullmann type C–N coupling followed by intramolecular cross-dehydrogenative coupling reaction in moderate to good yields. The synthesized compounds were tested for in vitro antibacterial activity against three Gram negative (Escherichia coli, Pseudomonas putida, and Salmonella typhi) and two Gram positive (Bacillus subtilis, and Staphylococcus aureus) bacteria. Among all tested compounds, 8ga, 8gc, and 8gd exhibited promising minimum inhibitory concentration (MIC) values (4–8 μg/mL) for all bacterial strains tested as compared to the positive control ciprofloxacin. The synthesized compounds were also evaluated for their in vitro antifungal activity against Aspergillus niger and Candida albicans and compounds 8ga, 8gc, and 8gd having potential antibacterial activity also showed pronounced antifungal activity (MIC values 8–16 μg/mL) against both strains. The bactericidal assay by propidium iodide and live–dead bacterial cell screening using a mixture of acridine orange/ethidium bromide (AO/Et·Br) showed considerable changes in the bacterial cell membrane, which might be the cause or consequence of cell death. Moreover, the hemolytic activity for most potent compounds (8ga, 8gc, and 8gd) showed their safety profile toward human blood cells.

Acridine orange

Aspergillus niger

Ethidium bromide

Minimum bactericidal concentration

Gram-Positive Bacteria

Antimycobacterial

10.1021/acsomega.8b01592

Cite

Citations (53)