Qualification: 
Ph.D, MSc, BSc
chinchubose@am.amrita.edu

Dr. Chinchu Bose is currently working as a Senior Research Fellow at the Amrita School of Biotechnology. He obtained an M. Sc. degree (Biotechnology) from Bharathidasan University in 2006. He has experience as a quality assurance chemist, in the pharma industry for a short period dealing with pharmaceutical production and quality control. After joining the School, he worked on the extraction of medicinal plants and isolation and characterization of compounds and their bioactivity studies. He is well-versed with the modern analytical techniques and has developed certain protocols in this context. He also focuses on developing innovative methods for isolation of target-dependent compounds. He is well established with analytical process validations and maintenance of analytical instruments such as HPLC. One of his keen interest area is value addition to underutilized plant products and development of indigenous formulations for sericulture.

Educational Qualification

  • Ph. D., Amrita Vishwa Vidyapeetham (2019)
  • M.Sc., Biotechnology, Bharathidasan University (2006).
  • B.Sc., BioChemistry, Kerala University (2003).

Area of interest

  • Natural product chemistry- Isolation and Characterization.
  • DNA protectants, Antioxidants, Nitrioxide quenchers, Tyrosinase inhibitors.
  • Sericulture and rural development.
  • Method development for isolation and analysis.
  • Value addition to underutilized plants or plant products.

Experience

  • Quality assurance chemist Indchemi pharmaceuticals, Daman&Due.
  • Junior research fellow in DRDO project 2007.
  • Junior research fellow in DRDO project 2008.
  • Senior research fellow in DBT project 2009.

Training

  • Workshop on High Performance Liquid Chromatography Techniques held at the AmritaAgilent Research Center Amrita School of Biotechnology.
  • Undergone training in the division of Cancer Research at Regional Cancer Center, Thiruvananthapuram.

PROJECTS ONGOING

  • Isolation, characterization and screening of bioactive principles of medicinal plants .
  •  Value addition to underutilized biosources

CONTRIBUTIONS

BOOKS AND CHAPTER

Chinchu Bose, N. Pandurangan, Virendra Singh and A. Banerji.Isolation, Characterization and Chemical Fingerprinting of Bioactives from Indian Seabuckthorn (Hippophae L.)Species.Seabuckthorn (Hippophae L.) A Multipurpose Wonder Plant. Vol. IV: Emerging Trends in Research and Technologies, 2014, 262.

PATENT FILED

“A process for obtaining phytoecdysteroid rich extract”  (application no. 1441/del/2008)

Publications

Publication Type: Journal Article

Year of Publication Title

2019

Anupama Binoy, Nedungadi, D., Katiyar, N., Chinchu Bose, Dr. Sahadev Shankarappa, Dr. Bipin G. Nair, and Dr. Nandita Mishra, “Plumbagin induces paraptosis in cancer cells by disrupting the sulfhydryl homeostasis and proteasomal function”, Chemico-Biological Interactions, p. 108733, 2019.[Abstract]


Plumbagin (PLB) is an active secondary metabolite extracted from the roots of Plumbago rosea. In this study, we report that plumbagin effectively induces paraptosis by triggering extensive cytoplasmic vacuolation followed by cell death in triple negative breast cancer cells (MDA-MB-231), cervical cancer cells (HeLa) and non-small lung cancer cells (A549) but not in normal lung fibroblast cells (WI-38). The vacuoles originated from the dilation of the endoplasmic reticulum (ER) and were found to be empty. The cell death induced by plumbagin was neither apoptotic nor autophagic. Plumbagin induced ER stress mainly by inhibiting the chymotrypsin-like activity of 26S proteasome as also evident from the accumulation of polyubiquitinated proteins. The vacuolation and cell death were found to be independent of reactive oxygen species generation but was effectively inhibited by thiol antioxidant suggesting that plumbagin could modify the sulfur homeostasis in the cellular milieu. Plumbagin also resulted in a decrease in mitochondrial membrane potential eventually decreasing the ATP production. This is the first study to show that Plumbagin induces paraptosis through proteasome inhibition and disruption of sulfhydryl homeostasis and thus further opens up the lead molecule to potential therapeutic strategies for apoptosis-resistant cancers.

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2018

A. Vijayakumar, Ajith Madhavan, Chinchu Bose, Nanjan Pandurangan, Sindhu Shetty K., Archana Palillamvedu, Megha Prasad, Dr. Sanjay Pal, and Dr. Bipin G. Nair, “Potent Chitin Synthase Inhibitors from Plants”, Current Bioactive Compounds, vol. 14, 2018.

2017

Damu Sunilkumar, Chinchu Bose, Sanu K Shaji, Nanjan Pandurangan, Geetha B Kumar, Asoke Banerji, and Dr. Bipin G. Nair, “Coconut Shell Derived Bioactive Compound Oxyresveratrol Mediates Regulation Of Matrix Metalloproteinase 9”, International Journal of Pharma and Bio Sciences, vol. 8, no. 1, pp. 202 – 210, 2017.

2016

Dr. Jyotsna Nambiar, Chinchu Bose, Meera Venugopal, Dr. Asoke Banerji, T. B. Patel, Dr. Geetha Kumar, and Dr. Bipin G. Nair, “Anacardic acid inhibits gelatinases through the regulation of Spry2, MMP-14, EMMPRIN and RECK”, Experimental Cell Research, vol. 349, pp. 139-151, 2016.[Abstract]


Earlier studies from our laboratory have identified Anacardic acid (AA) as a potent inhibitor of gelatinases (MMP-2 and 9), which are over-expressed in a wide variety of cancers (Omanakuttan et al., 2012). Disruption of the finely tuned matrix metalloproteinase (MMP) activator/inhibitor balance plays a decisive role in determining the fate of the cell. The present study demonstrates for the first time, that in addition to regulating the expression as well as activity of gelatinases, AA also inhibits the expression of its endogenous activators like MMP-14 and Extracellular Matrix MetalloProteinase Inducer (EMMPRIN) and induces the expression of its endogenous inhibitor, REversion-inducing Cysteine-rich protein with Kazal motifs (RECK). In addition to modulating gelatinases, AA also inhibits the expression of various components of the Epidermal Growth Factor (EGF) pathway like EGF, Protein Kinase B (Akt) and Mitogen-activated protein kinases (MAPK). Furthermore, AA also activates the expression of Sprouty 2 (Spry2), a negative regulator of EGF pathway, and silencing Spry2 results in up-regulation of expression of gelatinases as well as MMP-14. The present study thus elucidates a novel mechanism of action of AA and provides a strong basis for utilizing this molecule as a template for cancer therapeutics.

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PDF iconanacardic-acid-inhibits-gelatinases-through-the-regulation-of-spry-2-mmp-14-emmprin-and-reck-11october2016.pdf

2016

A. Omanakuttan, Chinchu Bose, N., P., G. B. Kumar, A. Banerji, and Dr. Bipin G. Nair, “Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone”, Experimental Cell Research, vol. 346, no. 2, pp. 167-175, 2016.[Abstract]


The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′, 7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. © 2016

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PDF iconnitric-oxideand-erk-mediates-regulation-of-cellular-processes-by-ecdystrone-18july2016.pdf

2016

Shantikumar V Nair, Baranwal, G., Chatterjee, M., Sachu, A., Dr. Anil Kumar V., Chinchu Bose, Dr. Asoke Banerji, and Dr. Raja Biswas, “Antimicrobial Activity of Plumbagin, a Naturally Occurring Naphthoquinone from Plumbago Rosea, against Staphylococcus Aureus and Candida Albicans”, International Journal of Medical Microbiology, vol. 306, pp. 237-248, 2016.[Abstract]


Candida albicans and Staphylococcus aureus are opportunistic pathogens. Despite causing a number of independent infections, both pathogens can co-infect to cause urinary tract infections, skin infections, biofilm associated infections, sepsis and pneumonia. Infections of these two pathogens especially their biofilm associated infections are often difficult to treat using currently available anti-bacterial and anti-fungal agents. In order to identify a common anti-microbial agent which could confer a broad range of protection against their infections, we screened several phytochemicals and identified plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a phytochemical from Plumbago species as a potent antimicrobial agent against S. aureus and C. albicans, with a minimum inhibitory concentration of 5 μg/ml. Antimicrobial activity of plumbagin was validated using an ex-vivo porcine skin model. For better understanding of the antimicrobial activity of plumbagin, a Drosophila melanogaster infection model was used, where D. melanogaster was infected using S. aureus and C. albicans, or with both organisms. The fly's survival rate was dramatically increased when infected flies were treated using plumbagin. Further, plumbagin was effective in preventing and dispersing catheter associated biofilms formed by these pathogens. The overall results of this work provides evidence that plumbagin, possesses an excellent antimicrobial activity which should be explored further for the treatment of S. aureus and C. albicans infections.

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2016

S. Muzaffar, Chinchu Bose, Dr. Asoke Banerji, Dr. Bipin G. Nair, and B. B. Chattoo, “Anacardic acid induces apoptosis-like cell death in the rice blast fungus Magnaporthe oryzae”, Applied Microbiology and Biotechnology, vol. 100, no. 1, pp. 323-335, 2016.[Abstract]


<p>Anacardic acid (6-pentadecylsalicylic acid), extracted from cashew nut shell liquid, is a natural phenolic lipid well known for its strong antibacterial, antioxidant, and anticancer activities. Its effect has been well studied in bacterial and mammalian systems but remains largely unexplored in fungi. The present study identifies antifungal, cytotoxic, and antioxidant activities of anacardic acid in the rice blast fungus Magnaporthe oryzae. It was found that anacardic acid causes inhibition of conidial germination and mycelial growth in this ascomycetous fungus. Phosphatidylserine externalization, chromatin condensation, DNA degradation, and loss of mitochondrial membrane potential suggest that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that anacardic acid induces caspase-independent apoptosis in M. oryzae. Expression of a predicted ortholog of apoptosis-inducing factor (AIF) was upregulated during the process of apoptosis, suggesting the possibility of mitochondria dependent apoptosis via activation of apoptosis-inducing factor. Anacardic acid treatment leads to decrease in reactive oxygen species rather than increase in reactive oxygen species (ROS) accumulation normally observed during apoptosis, confirming the antioxidant properties of anacardic acid as suggested by earlier reports. Our study also shows that anacardic acid renders the fungus highly sensitive to DNA damaging agents like ethyl methanesulfonate (EMS). Treatment of rice leaves with anacardic acid prevents M. oryzae from infecting the plant without affecting the leaf, suggesting that anacardic acid can be an effective antifungal agent. © 2015 Springer-Verlag Berlin Heidelberg</p>

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PDF iconanacardic-acid-induces-apoptosis-cell-death-rice-blast-fungus-magnaporthe-oryzae-3august2015.pdf

2014

S. Chittiyath Madhavan, Chinchu Bose, Mathew, T. Perakathus, and Dr. Asoke Banerji, “Indian medicinal plant, Coscinium fenestratum-A new bio source for the multifunctional bio active molecule–ecdysterone”, International Journal of Herbal Medicine, vol. 3, no. 1, pp. 9-12, 2014.[Abstract]


Phytochemical investigation on Coscinium fenestratum (Gaertn.) Collebr, an important Ayurvedic plant, revealed the presence of significant amounts of ecdysterone in the stem (0.22%) and leaves (0.12%), in addition to berberine. Ecdysterone was characterized using High Performance Liquid Chromatography (HPLC), Infrared Spectroscopy (FT-IR) and Liquid Chromatography-Mass Spectroscopy (LC-MS). Isolation of this multi- functional bioactive compound will throw light on the chemical basis for the various pharmacological effects of Coscinium plant extract.

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2013

A. Khan, Manna, K., Chinchu Bose, Sinha, M., Das, D. Kr., Kesh, S. Bandhu, Chakrabarty, A., Dr. Asoke Banerji, and Dey, S., “Gossypetin, a Naturally Occurring Hexahydroxy Flavone, Ameliorates Gamma Radiation-Mediated DNA Damage”, International Journal of Radiation Biology, vol. 89, pp. 965-975, 2013.[Abstract]


<p>AbstractPurpose: To evaluate the protective effect of gossypetin (GTIN) against gamma (γ)-radiation-mediated DNA damage.Materials and methods: Increasing concentrations (10–150 μM) of GTIN were incubated with supercoiled DNA 1 h prior exposure to γ-radiation in the range of 5-Gy absorbed dose from Co60 γ source. To establish the effective protective concentration of GTIN, supercoiled DNA was pre-incubated with 50 μM of GTIN for 1 h followed by exposure of 5, 10 and 20 Gy doses of γ-radiation. Moreover, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical, hydroxyl radical, nitric oxide (NO) scavenging, metal chelating activity and ferric reducing antioxidant power (FRAP) of GTIN were measured and compared with standards. The flowcytometric analysis and radiation-induced genomic DNA damage by comet assay were employed to estimate the level of intracellular reactive oxygen species (ROS) using isolated murine hepatocytes.Results: GTIN was able to effectively scavenge different free radicals in in vitro situations. It could significantly prevent radiation induced supercoiled and genomic DNA damage with reduced comet parameters. It also acted as a potent scavenger of the radiation induced ROS.Conclusions: GTIN ameliorated radiation-induced oxidative stress and DNA damage by its free-radical scavenging activity.</p>

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2012

A. Omanakuttan, Dr. Jyotsna Nambiar, Rodney M. Harris, Chinchu Bose, Pandurangan Nanjan, Rebu K. Varghese, Geetha B. Kumar, John A. Tainer, Dr. Asoke Banerji, J. Jefferson P. Perry, and Dr. Bipin G. Nair, “Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9”, 2012.[Abstract]


Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that anacardic acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that anacardic acid binds into the MMP-2/9 active site, with the carboxylate group of anacardic acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1′ pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that anacardic acid directly inhibits substrate peptide cleavage in a dose-dependent manner, with an IC50&nbsp;of 11.11 μM. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic acid, and aspirin, all of which lack key functional groups present in anacardic acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by anacardic acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action.

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2011

Pandurangan Nanjan, Chinchu Bose, and A. Banerji, “Synthesis and Antioxygenic Activities of Seabuckthorn Flavone-3-ols and Analogs”, Bioorganic & Medicinal Chemistry Letters, vol. 21, pp. 5328 - 5330, 2011.[Abstract]


A practical synthesis of polyhydroxy- and regiospecifically methylated flavone-3-ols which are components of commercial ‘seabuckthorn flavone’ has been achieved by modified Algar–Flynn–Oyamada method. Antioxidant activities of seabuckthorn extracts, isolated products and a number of flavone-3-ols have been determined. Structure–activity relationships have been discussed. Amongst the compounds tested, gallic acid, which is also present in seabuckthorn, was found to be the most effective antioxidant and radioprotectant.

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Publication Type: Conference Paper

Year of Publication Title

2015

Damu Sunilkumar, Chinchu Bose, Sanu K Shaji, Dr. Asoke Banerji, Geetha B. Kumar, and Dr. Bipin G. Nair, “Cocos Nucifera Shell Extract Down Regulates MMP-2, MMP-9 and Cell Migration in A375 Cells (Poster)”, in The XXXIX All India Cell Biology Conference , 2015.[Abstract]


Melanoma is the least common but most fatal form of skin cancer. An essential step in melanoma cell migration, invasion, and metastasis is the degradation of basement membranes and extracellular matrix. Matrix metalloproteinases (MMPs) and their tissue inhibitors play a crucial role in these complex multistep processes. We investigated the effect of extract from coconut (Cocos nucifera) shell on human melanoma cell line A375. The coconut shell extract was fractionated and the bioactivity screening was carried out. The ethyl methyl ketone (EMK) extract, which was identified as being most potent was further purified to yield two main subfractions (F1 and F2). Comparative studies with gelatin zymography demonstrated that the ‘F1’ significantly down regulated the gelatinolytic activity of MMP-2 and MMP-9. Similarly ,the gene expression studies with ‘F1’ showed down regulation of MMP-2, MMP-9, VEGF and COX-2 all of which play key roles in metastasis, angiogenesis and tumor promoting inflammation. Further, studies confirmed that ‘F1’ inhibited migration and caused arrest at G2/M phase of the cell cycle. Susequently, the structural characterization by LC-MS/MS and NMR studies determined the active fraction, ‘F1’to be oxyresveratrol, a stilbenoid. Thus, we report for the first time the isolation and characterization of the compound, oxyresveratrol from coconut shell and also show its regulation of MMPs in human melanoma which suggests its therapeutic potential in cancer.

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2013

C. M. Sreejit, Kuthannur, S., Chinchu Bose, P, T. Mathew, and Banerji, A., “Application Of Indigenous Growth Regulators In Sericulture - A Field Study In Palakkad District, Kerala”, in International Conference on Biotechnology for Innovative Applications.Elsevier, 2013.

2013

Chinchu Bose and Dr. Asoke Banerji, “Bioactive Compounds from Underutilized Plants and Plant Products”, in International Conference on Biotechnology for Innovative Applications.Elsevier, Amrita Vishwa Vidyapeetham, Kollam, Kerala, India, 2013.

2013

A. Madhavan, S, S., Chinchu Bose, and Pandurangan Nanjan, “Screening, Production, Purification and Application of Naringenase Elaborated by Aspergillus Species of Section Nigri”, in International Conference on Biotechnology for Innovative Applications, Amrita Vishwa Vidyapeetham, Kollam, Kerala, 2013.

2013

Pandurangan Nanjan, Walter Schrenk, Chinchu Bose, and Dr. Asoke Banerji, “Isolation, Charecterization Of Bioactives From The Indian Seabuckthorn”, in The Sixth Conference Of International Seabuckthorn Association, Potsdam2013, Germany ISA , 2013.

2013

Pandurangan Nanjan, Chinchu Bose, Walter Schrenk, and Dr. Asoke Banerji, “Value addition to unutilized Indian plants & plant products”, in 14th Asian Symposium on Medicinal Plants, Karachi, 2013.

2011

Chinchu Bose and A. Banerji, “Standardization of Bioactive Constituents of Seabuckthorn Extracts- Comparitive Phytochemical Study of Hippophaerhamnoides, H. Salicifolia and H. Sinensis”, in National conference on Seabuckthorn: Emerging trends in R&D on health protection and environmental conservation. , Himachal Pradesh krishivishvavidyalaya,Palampur, 2011.

2011

N. Pandurangan, Banerji, A., and Chinchu Bose, “Isolation and synthesis of Bioactive Flavonols from Indian Seabuckthorn”, in 5th International Seabucktorn Association Conference, Quinghai, 2011.[Abstract]


Isolation, Characterization and synthesis of bioactive flavanols from seabuckthorn. Poster presentation medicinal chemistry in India.

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2010

Chinchu Bose, Pandurangan Nanjan, and A. Banerji, “Isolation and Characterization of Bioactive Constituents of Himalayan (Ladakh) Seabuckthorn”, in National Conference on seabuckthorn : emerging trends in production to consumption, CSK Himachal Pradesh Agricultural University Palampur (H.P.). , 2010.

2010

Pandurangan Nanjan, Chinchu Bose, and A. Banerji, “Anti-Oxidants from Common Plants”, in U.G.C. sponsored National seminar on Medicinal plants and Pharmacopia., kollam, 2010.

2009

Chinchu Bose and Dr. Asoke Banerji, “Drug Discovery Through Seabuckthorn Research Invited presentation”, in fourth international Sea-buckthorn association conference (ISA 2009) Seabuckthorn on the way between science and industry interaction, Belokuriha, Russia, 2009.

2009

Chinchu Bose and Banerji, A., “Drug Discovery ThroughSeabuckthorn Research”, in Fourth international Sea-buckthorn association conference (ISA 2009) , Belokuriha, Russia, 2009.

Publication Type: Book Chapter

Year of Publication Title

2014

Pandurangan Nanjan, Chinchu Bose, Singh, V., and Dr. Asoke Banerji, “Isolation, Characterization and Chemical Fingerprinting of Bioactives from Indian Seabuckthorn (Hippophae L.) Species”, in Seabuckthorn (Hippophae L.) : A Multipurpose Wonder Plant : Vol. IV: Emerging Trends in Research and Technologies, vol. 4, 2014, p. 262.

Publication Type: Conference Proceedings

Year of Publication Title

2012

Pandurangan Nanjan, Chinchu Bose, and Dr. Asoke Banerji, “Synthesis and Antioxigenic Activities of Seabuckthorn and analogs flavones-3- ols”, National seminar on M odern trends in organic chemistry. Dept of Chemistry, Baselius College, Kottayam , 2012.

2011

Chinchu Bose and A. Banerji, “Comparitive Study Of Chemical Components Of HippophaeRhamnoides And H.Salicifolia”, National symposium on Innovative and modern technologies for agricultural productivity, food security and environmental management . The society for applied biotechnology, Mangalore, Karnataka. , 2011.

2011

S. C.M., Chinchu Bose, Pandurangan Nanjan, P., T. Mathew, and A. Banerji, “Bioprospection of Kerala flora for Phytoecdysoids : Value addition to biodiversity”, National symposium on Innovative and modern technologies for agricultural productivity, food security and environmental management . The society for applied biotechnology, Mangalore, Karnataka, 2011.

2011

Chinchu Bose, Pandurangan Nanjan, and A. Banerji, “Isolation, Characterization and synthesis of Bioactive flavanols from seabuckthorn”, Poster presentation Medicinal chemistry in India. Med chem. Congress. NIPER/IICT,Hyderabad, India, 2011.

2010

O. A, Chinchu Bose, A, B., and B, N., “Phytoecdysterone Mediated Potentiation of Wound Healing in Vitro: Possible Role for Nitric Oxide”, 79th SBCI meeting. IISc, Bangalore, 2010.

2007

Dr. Asoke Banerji, Sumitra, T. V., and Chinchu Bose, “Polar Constituents of Himalayan (Ladakh) Seabuckthorn leaves”, Proceedings of the 3rd International Seabuckthorn Association Conference, Ed. D. B. McKenzie. Laval University, Quebeck, Canada, p. 119, 2007.