| Educational
Qualification |
B.Sc
(Hons) Chemistry – S.A, Jaipuria College, Calcutta, Calcutta University
M.Sc
(Chemistry) – Dept. of Chemistry (Organic Chemistry), Calcutta University
Ph.D
(Biochemistry) – Bose Institute, Jadavpur University
1. Das A, Sinha S, Paul P, Acharya, B, Bhattacharyya, B and Chakrabarti, G. Deuterium Oxide stabilizes conformation of tubulin: A Biophysical and Biochemical study”. BMB Reports 41(1), 62-67, 2008.
2. Acharya, B., Bhattacharyya, B., and Chakrabarti, G. The natural naphthoquinone plumbagin exhibits antiproliferative activity and disrupts the microtubule network through tubulin binding. Biochemistry 47, 7838-7845, (2008). (Highly accessed)
3. Bandhu, A., Ganguly, T., Chanda, P. K., Das, M., Jana, B., Chakrabarti G., and Sau, S. (. Na+ and Mg2+ have antagonistic effects on the structure, function and stability of mycobacteriophage L1 repressor. BMB Reports 42, 293-298, (2009).
4.Das, A, Bhattacharya, A., and Chakrabarti, G. Cigarette smoke extract induces disruption of structure and function of
tubulin-microtubule in lung epithelium cells and in vitro. Chem. Res. Toxicol. (ACS publication). 22, 446-459, (2009). 5. Acharya, B., Chaudhuri D, Das, A, and Chakrabarti, G. Vitamin K3 Disrupts the Microtubule Networks By Tubulin Binding: A Novel Mechanism of Its Antiproliferative Activity. Biochemistry 48, 6863-6874, (2009).
6.Mukherjee, S., Acharya, B., Bhattacharyya, B., and Chakrabarti, G. Genistein Arrests Cell Cycle Progression of A549 cells at G2/M And Depolymerizes Interphase Microtubules Through Binding to a Unique Site of Tubulin. Biochemistry, 49, 1702-1712, (2010).
7. Das, A., Chakrabarty, S., Chaudhury, D., and Chakrabarti, G. 1,4-Benzoquinone (PBQ) induced toxicity in lung epithelial cells is mediated by the disruption of the Microtubule network and activation of Caspase-3. Chem. Res. Toxicol. (ACS publication) 23(6), 1054-1066, (2010).
8. Chaudhury, D., Das, A., Bhattacharya, A., and Chakrabarti, G. Aqueous extract of ginger shows antiproliferative activity through disruption of microtubule network of cancer cells. Food and Chemical Toxicology 48(10), 2872-2880, (2010).
9. Chanda PK, Bandhu A, Jana B, Mondal R, Ganguly T, Sau K, Lee CY, Chakrabarti G, Sau S. Characterization of an unusual cold shock protein from Staphylococcus aureus. J Basic Microbiol. 50, 519-526, (2010).
10. Deb T, Choudhury D, Guin PS, Saha MB, Chakrabarti G*, and Das S*. A complex of Co(II) with 2-hydroxyphenyl-azo-2-naphthol (HPAN) is far less cytotoxic than the parent compound on A549-lung carcinoma and peripheral blood mononuclear cells: Reasons for reduction in cytotoxicity. Chem Biol Interact.189, 206-14, (2011). (* Joint corresponding authors).
11.Chakrabarty S, Das A, Bhattacharya A, and Chakrabarti G. Theaflavins Depolymerize Microtubule Network through Tubulin Binding and Cause Apoptosis of Cervical Carcinoma HeLa Cells. J Agric Food Chem. 59, 2040-2048, (2011). 12. Acharya B,
Bhattacharyya, S., Choudhury, D., and Chakrabarti, G. The microtubule depolymerizing agent naphtazarin
induces both apoptosis and autophagy in A549 lung cancer cells. Apoptosis 16, 924-939, (2011).
Development
of anti-tumor agent from natural compounds targeting tubulin-microtubule
system, a major cytoskeleton protein.
Tubulin-microtubule
has very important role in cell division. Because it is
dynamic in nature and participates in mitosis, it has been
one most successful drug target in cancer chemotherapy.
Taxol, which stabilized microtubule
and disrupts microtubule dynamics, one of the most successful
anti-cancer drug, has been used for treatment of ovarian, breast and non-small
cell lung carcinomas. Vinka
alkaloid (vinblastine, vincristine),
which inhibits tubulin polymerization into microtubule,
is used for actuate lymphoblastic leukemia (ALL) and other pediatric malignancies.
But drug resistance and toxicity remains a significant problem
in treatment of malignancies with taxol
and vinka alkaloids. We need to develop new anti-tumor
drug which would be more potent and less toxic to normal
cells.
We are working on development
of potential microtubule inhibitors which could be used
for anti-cancer therapy. We got good results in cancer cell
lines experiments with some of the agents.
We
have found many compounds as well as extracts that act as
antimitotic agent, like; Plumbagin
(5-hydroxy-2-methyl-1, 4-naphthoquinone), a naphthoquinone
isolated from the roots of Plumbaginaceae
plants and many other flavones, flavonoids,
naphthoquinones and other naturally occurring poly phenols.
Normal
cell cycle phase distribution of HeLa
cells (A), G2/M arrest of cell cycle (B) and cellular apoptosis
(C) upon drug treatment.
(A)
Control A549 cells with nicely grown interphase microtubule,
cells with altered cellular cytoskeletal structure and (B)
antimitotic targeted compound treated disrupted microtubule
structure.
Expression
of tubulin isotypes for understanding mechanism of drug-resistance and
development in cancer
Tubulin
is a cell division protein many drugs have been targeted
to tubulin for the arrest of microtubule dynamics, as a
measure of treatment of cancer. The main problem in cancer
treatment is the resistance of the cancer to the chemotheraupeutic drug.
There
are six isotypes of α- tubulin and seven isotypes of
β-tubulin so far known in human. The expression of
different tubulin isotype is tissue specific. In general
in cancerous cell line, overexpression of some β-tubulin
isotypes has been observed. It is not known till date that
by what mechanism tumors become resistant to drugs. It is
believed that increase of specific tubulin isotype (bIII)
or mutation of a or b may cause resistance to such drugs.
Due to this, development of a mammalian tubulin expression
system in baculovirus-insect cells may not only help to
solve this long standing problem but also provide a target
model system to develop new potential anti-tumor drug. Thus
based upon this study, new drugs could be designed and synthesized
with the help of synthetic chemistry.
Expression
of Plasmodium falciparum
tubulin in baculovirus-insect cell system for development of anti-malarial
drug’
Malaria
is the world's most important tropical disease. In India
and in sub-Saharan Africa,
Malaria exacts an enormous toll in lives, in medical costs,
and in days of labor lost. Among four human malarial parasites,
Plasmodium falciparum is the predominant cause of
mortality but drug resistance strains are major problem
of treatment of malaria. In India, 65% Plasmodium falciparum
strains are resistant to chloroquine, a commonly used drug
for treatment of malaria. This indeed calls for the quest
of new and more effective chemotherapeutic agents to combat
the disease. Our plan would be to attempt to develop a new
anti-malaria drug by targeting tubulin, a major cytoskeleton
protein. For studying drug binding, protein in the scale
of milligrams is required. We project have cloned tubulin
of Plasmodium falciparum into baculovirus-insect
cell vector for expression of the protein in insect cell
(Sf9). After purification of protein attempts would be made
to screen drugs that specifically bind Plasmodium falciparun
tubulin but not mammalian tubulin.
Tubulin-Microtubule
is the prime target for various environmental pollutants
and toxicants in cells
|
Control
lung epithelial cells
|
AECS
treated rounded cells |
The
disruption of the cellular microtubules leads to apoptosis
of the mammalian cells. Tubulin-Microtubule may be a major
target for various environmental pollutants and toxic chemicals
which result in cell damage and apoptosis. Treatment of
the lung epithelial cells with the aqueous extract of cigarette
smoke (AECS) results in the loss of their regular shape
and morphology and the cells become rounded.
We
have already established that tubulin cytoskeleton is the
prime target for the aqueous extract of cigarette smoke
(AECS), which causes extensive damage of the lung tissue
Consumption
of smokeless tobacco leads to the damage of the oral epithelial
cells. Tubulin-microtubule is found to be a potential target
for smokeless tobacco extract (SLT) and it is one of the
mechanisms of the SLT induced damage of the oral tissue.
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Subhendu
Chakrabarty
PhD
student (junior research fellow)
scmcba83@gmail.com
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Diptiman Choudhury
PhD
student (senior research fellow)
diptiman.choudhury@gmail.com
|
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Bipul
R. Acharya
PhD
student (senior research fellow)
BIPULACHARYA@gmail.com
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AmlanDas
PhD
student (senior research fellow)
amlan.das@gmail.com
|
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Sumita Mukherjee
PhD
student (senior research fellow)
sumitabiochem@gmail.com
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Avijit
Bhattacharyya
PhD
student (Senior research
fellow)
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