BIOMAT Database Logo BIOMAT Database Logo

Development of Novel Bis(indolyl)-hydrazide-Hydrazone Derivatives as Potent Microtubule-Targeting Cytotoxic Agents against A549 Lung Cancer Cells. 2016

Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
Department of Biotechnology and Dr. B. C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta , 35 Ballygunge Circular Road, Kolkata, WB 700 019, India.

The biological significance of microtubules makes them a validated target of cancer therapy. In this study, we have utilized indole, an important pharmacological scaffold, to synthesize novel bis(indolyl)-hydrazide-hydrazone derivatives (NMK-BH compounds) and recognized NMK-BH3 as the most effective one in inhibiting A549 cell proliferation and assembly of tissue-purified tubulin. Cell viability experiments showed that NMK-BH3 inhibited proliferation of human lung adenocarcinoma (A549) cells, normal human lung fibroblasts (WI38) and peripheral blood mononuclear cells (PBMC) with IC50 values of ∼2, 48.5, and 62 μM, respectively. Thus, the relatively high cytotoxicity of NMK-BH3 toward lung carcinoma (A549) cells over normal lung fibroblasts (WI38) and PBMC confers a therapeutic advantage of reduced host toxicity. Flow cytometry, Western blot, and immunofluorescence studies in the A549 cell line revealed that NMK-BH3 induced G2/M arrest, mitochondrial depolarization, and apoptosis by depolymerizing the cellular interphase and spindle microtubules. Consistent with these observations, study in cell free system revealed that NMK-BH3 inhibited the microtubule assembly with an IC50 value of ∼7.5 μM. The tubulin-ligand interaction study using fluorescence spectroscopy indicated that NMK-BH3 exhibited strong and specific tubulin binding with a dissociation constant of ∼1.4 μM at a single site, very close to colchicine site, on β-tubulin. Collectively, these findings explore the cytotoxic potential of NMK-BH3 by targeting the microtubules and inspire its development as a potential candidate for lung cancer chemotherapy.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D008870 Microtubules Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS. Microtubule
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003603 Cytotoxins Substances that are toxic to cells; they may be involved in immunity or may be contained in venoms. These are distinguished from CYTOSTATIC AGENTS in degree of effect. Some of them are used as CYTOTOXIC ANTIBIOTICS. The mechanism of action of many of these are as ALKYLATING AGENTS or MITOSIS MODULATORS. Cytolysins,Cytotoxic Agent,Cytotoxic Agents,Cytotoxin,Agent, Cytotoxic
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast

Related Publications

Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
Novel bis(indolyl)hydrazide-hydrazones as potent cytotoxic agents.
January 2012, Bioorganic & medicinal chemistry letters,
Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
Synthesis, antiproliferative and apoptosis induction potential activities of novel bis(indolyl)hydrazide-hydrazone derivatives.
March 2019, Bioorganic & medicinal chemistry,
Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
A facile synthesis of novel bis-(indolyl)-1,3,4-oxadiazoles as potent cytotoxic agents.
November 2012, ChemMedChem,
Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
Potent hydrazone derivatives targeting esophageal cancer cells.
March 2018, European journal of medicinal chemistry,
Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
Synthesis of novel ribavirin hydrazone derivatives and anti-proliferative activity against A549 lung cancer cells.
July 2009, Carbohydrate research,
Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
Synthesis and structure-activity relationships of novel 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide hydrazone derivatives as potential agents against A549 lung cancer cells.
November 2008, European journal of medicinal chemistry,
Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
Novel boronic acid derivatives of bis(indolyl) methane as anti-MRSA agents.
May 2017, Bioorganic & medicinal chemistry letters,
Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
Synthesis of novel substituted pyrazole-5-carbohydrazide hydrazone derivatives and discovery of a potent apoptosis inducer in A549 lung cancer cells.
March 2009, Bioorganic & medicinal chemistry,
Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
Bakuchiol derivatives as novel and potent cytotoxic agents: a report.
March 2012, European journal of medicinal chemistry,
Dipanwita Das Mukherjee, and N Maruthi Kumar, and Mukund P Tantak, and Amlan Das, and Arnab Ganguli, and Satabdi Datta, and Dalip Kumar, and Gopal Chakrabarti
Novel potent organoselenium compounds as cytotoxic agents in prostate cancer cells.
December 2007, Bioorganic & medicinal chemistry letters,
Copied contents to your clipboard!