Department of Biological Sciences
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Item Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies(Bentham Science, 2019) Chowdhury, Rajdeep; Shukla, Paritosh; Sharma, AshokBackground: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.Item Evaluation of novel platinum(ii) based AIE compound-encapsulated mesoporous silica nanoparticles for cancer theranostic application(RSC, 2018) Chowdhury, Rajdeep; Laskar, Inamur RahamanAdvanced biomedical research has established that cancer is a multifactorial disorder which is highly heterogeneous in nature and responds differently to different treatment modalities, due to which constant monitoring of therapy response is becoming extremely important. To accomplish this, different theranostic formulations have been evaluated. However, most of them are found to suffer from several limitations extending from poor resolution, radiation damage, to high costs. In order to develop a better theranostic modality, we have designed and synthesized a novel platinum(II)-based ‘aggregation induced emission’ (AIE) molecule (named BMPP-Pt) which showed strong intra-cellular fluorescence and also simultaneously exhibited potent cytotoxic activity. Due to this dual functionality, we wanted to explore the possibility of using this compound as a single molecule based theranostic modality. This compound was characterized using elemental analysis, NMR and IR spectroscopy, mass spectrometry and single crystal X-ray structure determination. BMPP-Pt was found to exhibit a high AIE property with emission maxima at 497 nm. For more efficient cancer cell targeting, BMPP-Pt was encapsulated into mesoporous silica nanoparticles (Pt-MSNPs) and the MSNPs were further surface modified with an anti-EpCAM aptamer (Pt-MSNP-E). Pt-MSNPs exhibited higher intracellular fluorescence compared to free BMPP-Pt, though both of them induced a similar degree of cell death via the apoptosis pathway, possibly via cell cycle arrest in the G1 phase. Anti-EpCAM aptamer modification was found to increase both cytotoxicity and intracellular fluorescence compared to unmodified MSNPs. Our study showed that EpCAM functionalized BMPP-Pt loaded MSNPs can efficiently internalize and induce apoptosis of cancer cells as well as show strong intracellular fluorescence. This study provides clues towards the development of a potential single compound based theranostic modality in future.Item Functional Autophagic Flux Regulates AgNP Uptake And The Internalized Nanoparticles Determine Tumor Cell Fate By Temporally Regulating Flux(Dove Press, 2019) Pande, Surojit; Chowdhury, RajdeepSilver nanoparticles (AgNPs) are known to induce the conserved, cellular, homeostatic process- autophagy in tumor cells. Previous studies primarily focus on the pro-survival role of autophagy post AgNP exposure in tumor cells, but seldom on its role in AgNP uptake, or on the functional significance of autophagy temporal dynamics. Our study sheds more light on the extensive crosstalk that exists between AgNP and autophagy, which can be critical to the improvement of AgNP-induced therapeutic effectsItem A New Aggregation Induced Emission Active Halochromic White Light Emissive Molecule: Combined Experimental and Theoretical Study(RSC, 2020) Chowdhury, Rajdeep; Laskar, Inamur Rahaman; Roy, Ram KinkarRed/near infrared-emissive organic molecules that are aggregation induced emission (AIE) active and having a pH-sensitive core are high in-demand for real-world applications. We have designed and synthesized a far-red to near infrared (NIR) fluorogenic donor–acceptor (D–A) type probe 4-((4-(2-(3,3-dimethyl-3H-indole-2-yl)vinyl)phenyl)(phenyl)amino)benzaldehyde (TPA-SCY), that can undergo protonation with a stronger intramolecular charge transfer. The molecule is pH-sensitive and responds to the acidic behavior of chloroform to produce a unique halochromic white-light emission. Owing to its sensitivity toward pH and its highly emissive nature in the red/NIR region at low pH (approximately 3–5), it accumulates in the intracellular lysosomes and can be used as a live-tracker for lysosomes. Successful application of time-dependent density functional theory with the use of an optimally tuned range-separated hybrid functional reproduces the experimental absorption and emission spectra within the 1–5 nm range (which is not observed when conventional range-separated hybrid functionals are used). Thus, the present work embodies synthesis and photophysical studies (supported by an efficient and highly accurate theoretical tool) of a new AIE active halochromic white light emissive molecule with extensive charge transfer properties and having the ability to behave as a live LysoTracker.Item Engineering a light-driven cyanine based molecular rotor to enhance the sensitivity towards a viscous medium(RSC, 2021) Chowdhury, Rajdeep; Laskar, Inamur Rahaman; Majumder, Syamantak; Mukherjee, SudeshnaThis article describes the enhanced sensitivity to a viscous medium by a molecular rotor based fluorophore (RBF), TPSI I. The TPSI I molecule is designed in such a way that it consists of a rotor and a fluorophore with a π-rich bridge between them. TPSI I is a light-responsive material in solution as well as in the solid state. The structural design of the molecule allows flexible rotation and photo-induced cis–trans isomerization both in the solid state as well as in solution. These combined attributes of TPSI I are responsible for the ultrasensitive viscosity response of the new material, which was verified through the Förster–Hoffmann equation. According to this equation, the derived ‘x’ value is 1.02 (x is related to the sensitivity) which is the highest among the contemporary reports for RBFs. The facts were evidenced both by experimental as well as theoretical data. The ultrasensitivity towards viscosity was further analyzed in in vitro studies by detecting the subtle changes in the alteration of intracellular viscosity in normal and cancerous cells. An alteration of intracellular viscosity in cells treated with viscosity modulators was also confirmed using a previously well-established viscosity measurement technique, dynamic measurement through the piezoelectric patch. Our research offers a detailed mechanism to improve viscosity sensors and an efficient probe for detecting minute changes in intracellular viscosity.Item Synthesis and evaluation of bile acid amides of [Formula: see text]-cyanostilbenes as anticancer agents(Springer, 2017) Jha, Prabhat N.; Chowdhury, Rajdeep; Sakhuja, RajeevA series of amino-substituted α-cyanostilbene derivatives and their bile acid (cholic and deoxycholic acid) amides were designed and synthesized. A comparative study on the anticancer and antibacterial activity evaluation on the synthesized analogs was carried against the human osteosarcoma (HOS) cancer cell line, and two gram −ve (E. coli and S. typhi) and two gram +ve (B. subtilis and S. aureus) bacterial strains. All the cholic acid α-cyanostilbene amides showed an IC50 in the range 2–13 μM against human osteosarcoma cells (HOS) with the most active analog (6g) possessing an IC50 of 2μM. One of the amino-substituted α-cyanostilbene, 4e, was found to possess an IC50 of 3μM. An increase in the number of cells at the sub-G1 phase of the cell was observed in the in vitro cell cycle analysis of two most active compounds in the series (4e, 6g) suggesting a clear indication toward induction of apoptotic cascade. With respect to antibacterial screening, amino-substituted α-cyanostilbenes were found to be more active than their corresponding bile acid amides. The synthesized compounds were also subjected to in silico study to predict their physiochemical properties and drug-likeness score.