Department of Chemistry
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Item Solvatochromic study of three indoloquinoline derivatives: Effect of chloro group/s on the photophysics of thecompound(Elsiever, 2011-01) Kumar, DalipPhotophysical modulations of three indoloquinoline derivatives, viz., 5-Methyl-5H-indolo[3,2-c]quinoline (MIQ), 8-Chloro-5-methyl-5H-indolo[3,2-c]quinoline (CMIQ), and 2,8-Dichloro-5-methyl-5H-indolo[3,2-c]quinoline (DCMIQ) have been studied. These compounds belong to the cryptosanguinolentine family and are known to have potential anti-cancer abilities. In the present work we studied the effect of solvent polarity on introduction of one or two chloro (-Cl) group/s at chosen sites on the parent cryptosanguinolentine. The compounds exist mainly in two forms, neutral and zwitterionic, in equilibrium at ground state. Interestingly, all the three compounds exhibit hypsochromic shift in their absorption and fluorescence spectra with increase in relative permittivity of solvents in most of the cases. Blue-shift in fluoroscence might be due to lesser dipole moment of the species in the excited state. Time-resolved fluorescence spectroscopy clearly indicates the presence of two species in all the solvents in the excited state (except MIQ in water). The shift in the molecular polarity with chloro substitution/s seems to be responsible for the contributions of the two species in the excited state. The relative contributions are found to alter remarkably in a regular manner when MIQ is compared with CMIQ and DCMIQ. This behavior is supposed to be mainly due to dipole–dipole interaction between the solvent molecules and the fluorophores.Item Development of Novel Bis(indolyl)-hydrazide–Hydrazone Derivatives as Potent Microtubule-Targeting Cytotoxic Agents against A549 Lung Cancer Cells(ACS, 2016-04-25) Kumar, DalipThe 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.Item Fluorescence spectroscopic studies on substituted porphyrins in homogeneous solvents and cationic micellar medium(Elsiever, 2013-02) Kumar, Anil; Kumar, DalipSteady state and time-resolved fluorescence properties of porphyrin appended 1,3,4-oxadiazoles and thiazoles were described in homogeneous medium as well as in presence of cationic surfactant cetyltrimethylammonium bromide (CTAB). The electron withdrawing substituent on the porphyrin moiety in both the cases make a donor–spacer–acceptor type of intramolecular photoinduced electron transfer (PET) system resulting substantial quenching in porphyrin fluorescence due to partial energy migration towards the acceptor in the excited state. The increase in fluorescence yield as well as appreciable difference in fluorescence decay behavior in aqueous buffer solution of pH 4.2 from that in chloroform solution is believed due to partial protonation of the porphyrin ring. All the investigated systems show preferential binding into the interfacial region of the micellar sub-domain with varying degree of penetration depending on the nature of the substituent. Almost 2–4 fold increase in fluorescence yield for the probes is explained on the basis of restricted flexibility and corresponding decrease in total nonradiative rate inside the micellar interface layer.