Bishnu Prasad Joshi
Amherst, Massachusetts, United States
1K followers
500 connections
About
I am a chemical biologist and a biomaterials scientist with a multidisciplinary skill set…
Activity
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I am honored to be the recipients of the 2024 Fall Travel Award! 🎉 A big thank you to the Postdoc Office and the selection committee for this…
I am honored to be the recipients of the 2024 Fall Travel Award! 🎉 A big thank you to the Postdoc Office and the selection committee for this…
Liked by Bishnu Prasad Joshi
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I enjoyed the Reverse Roundtables at the 2024 SSP New Directions in Scholarly Publishing Seminar today. We had a chance to spend time with our…
I enjoyed the Reverse Roundtables at the 2024 SSP New Directions in Scholarly Publishing Seminar today. We had a chance to spend time with our…
Liked by Bishnu Prasad Joshi
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Getting into r-HPLC Method development & Method validation for estimation of pharmaceutical drugs.Under senior scientist Dr. sajan…
Getting into r-HPLC Method development & Method validation for estimation of pharmaceutical drugs.Under senior scientist Dr. sajan…
Liked by Bishnu Prasad Joshi
Experience
Education
Volunteer Experience
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Founding Member
NIRI Nepal
- Present 3 years 10 months
Science and Technology
Science communication, participate in meetings and webinars, pitch in ideas to improve research and development.
Publications
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Diarylidene-N-Methyl-4-Piperidone and Spirobibenzopyran Curcumin Analogues as Antioxidant and Anti-Inflammatory Pharmacophores
Cambridge: Cambridge Open Engage
Curcumin has well-known anti-oxidant properties, resulting from its radical scavenging ability and inhibition of inflammation-associated factors. However, its lack of solubility, instability, and poor bioavailability and biodistribution characteristics are an impediment to its use. To circumvent these issues while retaining curcumin’s biological activity, we synthesized twenty-one diarylidene-N-methyl-4-piperidones (DANMPs), four diheteroarylidene-N-methyl-4-piperidones (DHANMPs), and five…
Curcumin has well-known anti-oxidant properties, resulting from its radical scavenging ability and inhibition of inflammation-associated factors. However, its lack of solubility, instability, and poor bioavailability and biodistribution characteristics are an impediment to its use. To circumvent these issues while retaining curcumin’s biological activity, we synthesized twenty-one diarylidene-N-methyl-4-piperidones (DANMPs), four diheteroarylidene-N-methyl-4-piperidones (DHANMPs), and five spirobibenzopyran (SBP) derivatives. All were screened in terms of anti-oxidant activity via a cell-free 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and for drug-like properties in silico. In the former, some compounds possessed improved radical scavenging behavior versus ascorbic acid, which was used as a benchmark. Conformity to simulated Lipinski’s parameters and Absorption, Distribution, Metabolism, and Excretion (ADME) studies indicated the DANMPs, DHANMPs, and SBPs to be potentially useful compounds. A subset of molecules was investigated in terms of their aqueous solubilities, which were significantly improved compared to that of curcumin. In vitro assessments of the cellular and anti-inflammatory effects of these compounds were conducted using RAW264.7 macrophages. RT-PCR and Griess assays were used to evaluate the presence of inflammatory/activated (M1) markers and production of nitric oxide (NO) species, which are associated with inflammation, respectively. While the compounds did not affect non-stimulated (naïve) macrophages, they did reduce levels of markers and NO to extents similar to or better than curcumin in inflamed cells. Our results indicate that these pharmacophores possess anti-inflammatory properties and can be used as curcumin-substitutes with improved characteristics. Further investigation into their mechanisms of action and potential use in the treatment of inflammatory diseases is merited.
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Macrophage-Encapsulated Bioorthogonal Nanozymes for Targeting Cancer Cells
ACS JACS au
Macrophages migrate to tumor sites by following chemoattractant gradients secreted by tumor cells, providing a truly active targeting strategy for cancer therapy. However, macrophage-based delivery faces challenges of cargo loading, control of release, and effects of the payload on the macrophage vehicle. We present a strategy that employs bioorthogonal “nanozymes” featuring transition metal catalysts (TMCs) to provide intracellular “factories” for the conversion of prodyes and prodrugs into…
Macrophages migrate to tumor sites by following chemoattractant gradients secreted by tumor cells, providing a truly active targeting strategy for cancer therapy. However, macrophage-based delivery faces challenges of cargo loading, control of release, and effects of the payload on the macrophage vehicle. We present a strategy that employs bioorthogonal “nanozymes” featuring transition metal catalysts (TMCs) to provide intracellular “factories” for the conversion of prodyes and prodrugs into imaging agents and chemotherapeutics. These nanozymes solubilize and stabilize the TMCs by embedding them into self-assembled monolayer coating gold nanoparticles. Nanozymes delivered into macrophages were intracellularly localized and retained activity even after prolonged (72 h) incubation. Significantly, nanozyme-loaded macrophages maintained their inherent migratory ability toward tumor cell chemoattractants, efficiently killing cancer cells in cocultures. This work establishes the potential of nanozyme-loaded macrophages for tumor site activation of prodrugs, providing readily tunable dosages and delivery rates while minimizing off-target toxicity of chemotherapeutics.
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Synthesis, Mechanistic, and Synergy Studies of Diarylidenecyclohexanone Derivatives as New Antiplasmodial Pharmacophores
Medicinal Chemistry Research
Diarylidenecyclohexanone (DAC) derivatives (Ia-i, IIa-c and IIIa-b) were synthesized, characterized and screened for their in vitro antiplasmodial activities against erythrocytic stages of chloroquine (CQ) sensitive and resistant strains of P. falciparum by using SYBR green I fluorescence assay. SAR studies of DAC derivatives showed antiplasmodial activity in the order of 3-NO2 (Ib, IC50 0.95 µM) > 3-chloro (Id, IC50 3 µM) > 4-chloro (Ie, IC50 8.5 µM) > 2-chloro (Ic, IC50 13 µM)…
Diarylidenecyclohexanone (DAC) derivatives (Ia-i, IIa-c and IIIa-b) were synthesized, characterized and screened for their in vitro antiplasmodial activities against erythrocytic stages of chloroquine (CQ) sensitive and resistant strains of P. falciparum by using SYBR green I fluorescence assay. SAR studies of DAC derivatives showed antiplasmodial activity in the order of 3-NO2 (Ib, IC50 0.95 µM) > 3-chloro (Id, IC50 3 µM) > 4-chloro (Ie, IC50 8.5 µM) > 2-chloro (Ic, IC50 13 µM). Further Ib and Id exhibited nearly equal potencies against CQ-resistant strains P. falciparum Dd2, {IC50 1 µM (Ib) and 2.7 µM (Id)} and PfINDO {IC50 1.1 µM (Ib) and 2.5 µM (Id)}. Drug exposure followed by drug withdrawal-based stage-specific kill kinetic studies showed that Ib is shizonticidal within 3 h while the earliest killing actions against Trophozoites and Rings were seen at >3 h and >6 h, respectively. Combination studies of the most potent leads viz. Ib and Id showed strong to moderate synergistic effects with Artemisinin (ƩFIC50: 0.34 to 0.63) whereas no interaction (ƩFIC50: 0.65 to 2.36) was observed with Chloroquine. The DACs showed significant in silico binding affinity with β-haematin and P. falciparum lactate dehydrogenase (PfLDH) suggesting these to be the targets of their antiplasmodial action. High compliance with Lipinski rule of 5 and high selectivity index of Ib (105.3) and Id (8.3) against HeLa cell line indicated that Diarylidenecyclohexanones could serve as structural templates towards lead optimization of compounds for discovery of novel, potent, safe and affordable drugs against malaria.
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Surface-Modified Macrophages Facilitate Tracking of Breast Cancer-Immune Interactions
ACS Chemical Biology
The immune system has been found to play key roles in cancer development and progression. Macrophages are typically considered to be pro-inflammatory cells but can also facilitate pro-oncogenic activities via associations with tumors and metastases. The study of macrophages and their interactions within the context of cancer microenvironments is stymied by the lack of a system to track them. We present a cell-based strategy for studying cancer-immune cell interactions by chemically modifying…
The immune system has been found to play key roles in cancer development and progression. Macrophages are typically considered to be pro-inflammatory cells but can also facilitate pro-oncogenic activities via associations with tumors and metastases. The study of macrophages and their interactions within the context of cancer microenvironments is stymied by the lack of a system to track them. We present a cell-based strategy for studying cancer-immune cell interactions by chemically modifying the surfaces of macrophages with fluorophores. Two widely used methods are employed, affecting cell surface proteins and glycans via NHS-ester and Staudinger ligation reactions, respectively. We show that these modifications do not interfere with macrophage responses to chemoattractants and that interactions with cancer cells can be readily monitored. This work describes the development of macrophage-based imaging agents for tumor detection and assessment of interactions between immune cells and cancers.
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Harnessing Biology to Deliver Therapeutic and Imaging Entities via Cell‐Based Methods
Chemistry–A European Journal
The accumulation of therapeutic and imaging agents at sites of interest is critical to their efficacy. Similarly, off‐target effects (especially toxicity) are a major liability for these entities. For this reason, the use of delivery vehicles to improve the distribution characteristics of bio‐active agents has become ubiquitous in the field. However, the majority of traditionally employed, cargo‐bearing platforms rely on passive accumulation. Even in cases where “targeting” functionalities are…
The accumulation of therapeutic and imaging agents at sites of interest is critical to their efficacy. Similarly, off‐target effects (especially toxicity) are a major liability for these entities. For this reason, the use of delivery vehicles to improve the distribution characteristics of bio‐active agents has become ubiquitous in the field. However, the majority of traditionally employed, cargo‐bearing platforms rely on passive accumulation. Even in cases where “targeting” functionalities are used, the agents must first reach the site in order for the ligand–receptor interaction to occur. The next stage of vehicle development is the use of “recruited” entities, which respond to biological signals produced in the tissues to be targeted, resulting in improved specificities. Recently, many advances have been made in the utilization of cells as delivery agents. They are biocompatible, exhibit excellent circulation lifetimes and tissue penetration capabilities, and respond to chemotactic signals. In this Minireview, we will explore various cell types, modifications, and applications where cell‐based delivery agents are used.
Honors & Awards
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Dr. Paul Hatheway Terry Award for Outstanding Poster Presentation, 28th Annual ResearchFest Symposium, Dept. of Chemistry.
UMass Amherst
"Surface-Modification of Macrophages Imaging and Drug Delivery Vehicles", Outstanding Poster Presentation Award out of 100 plus posters presented by graduate students.
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Best Presentation Award at Integrated Chemistry Conference (ICCON).
Sri Sathya Sai Institute of Higher Learning
Oral presentation on “Synthesis, Characterization, and Anti-Malarial Activities of Dibenzylidene-Acetone and -Cycloalkanone Derivatives.”
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Award of Youth Leadership and Service Activities,
Sri Sathya Sai Seva Organization,
Award of Youth Leadership and Service Activities for distributing food and clothing in rural areas and for participating in old age home service activities in/around Kathmandu, Nepal -2010.
Languages
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English
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Nepali
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Hindi
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Sanskrit
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More activity by Bishnu Prasad
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Proud to be a part of the AMR Lab and the team that developed AMRx 😇 Congratulations to everyone!
Proud to be a part of the AMR Lab and the team that developed AMRx 😇 Congratulations to everyone!
Liked by Bishnu Prasad Joshi
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Polymers GRC 2025 program is live and we are accepting applications! https://lnkd.in/gBVDuRkD Thomas Epps, III and I look forward to welcoming you…
Polymers GRC 2025 program is live and we are accepting applications! https://lnkd.in/gBVDuRkD Thomas Epps, III and I look forward to welcoming you…
Liked by Bishnu Prasad Joshi
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