Browsing by Author "Satheeshkumar, Rajendran"

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    Experimental and theoretical physicochemical study of a new dispirocompound: 4′-(4-fluorophenyl)-2′,7-dimethyl-1,4-dihydro-3H-dispiro[cyclopent[b]indol-2,5′-[1,2]oxazinan-6′3"-indolin]-2",3-dione
    (2021) Satheeshkumar, Rajendran; Montecinos, Rodrigo; Vera, Ariesny; Prasad, Karnam Jayarampillai Rajendra; Kaminsky, Werner; Salas, Cristian O.
    We present Et3N mediated synthesis of a novel dispirocompound from 5-methyl-2-(4'-fluorophenylidine)-1-oxo-1,2,3,8-tetrahydrocyclopent[b]indole, isatin, and sarcosine through 1,3-dipolar cycloaddition reaction. The crystal structure of synthesised compound, 4'-(4-fluorophenyl)-2',7-dimethyl-1,4-dihydro-3H-dispiro[cyclopent[b]indol-2,5'-[1,2]oxazinan-6',3 ''-indolinl-2 '',3-dione is reported. FT-IR, H-1 and C-13 NMR chemical shifts as measured and calculated using B3LYP method with the 6-311G(d,p) basis set in gas phase were found in good agreement. The optimized geometry of the dispirocompound was compared with experimental XRD values. DFT calculations of the molecular electrostatic potential (MEP), Non-covalent interactions and Hirshfeld Surface analysis, Non-linear optical (NLO) properties and frontier molecular orbitals (FMO) identified chemically active sites of the dispirocompound responsible for its chemical reactivity. (C) 2020 Elsevier B.V. All rights reserved.
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    Friedlander Synthesis of Novel Polycyclic Quinolines Using Solid SiO2/H2SO4 Catalyst
    (2021) Satheeshkumar, Rajendran; Shanmugaraj, Krishnamoorthy; Delgado Aguilar, Thalia; Bertrand, Jeanluc; Brito, Iván; Salas Sánchez, Cristián Osvaldo
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    Small interfering RNA for cancer treatment: overcoming hurdles in delivery
    (2020) Zacconi, Flavia C. M.; Aljabali, Alaa A.A.; Chellappan, D.K.; Shrivastava, Garima; Gupta, Gaurav; Bakshi, Hamid A.; Dua, Kamal; Metha, Meenu; Tambuwala, Murtaza M.; Amnerkar, Nikhil D.; Charbe, Nitin Bharat; Negi, Poonam; Satheeshkumar, Rajendran; Khadse, Saurabh C.; Satija, Saurabh
    In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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    Solvent-Free Synthesis of New Quinoline Derivatives via Eaton's Reagent Catalysed Friedlander Synthesis
    (2022) Satheeshkumar, Rajendran; Prasad, Karnam Jayarampillai Rajendra; Wang Wen-Long; Espinosa-Bustos, Christian; Salas, Cristian O.
    An interest for the development of new 2-acetyl/propanoyl quinolines via Friedlander synthesis is one of the most studied synthetic approaches. Herein we report the use of a freshly prepared Eaton's reagent (phosphorus pentoxide in methanesulfonic acid) as catalyst without solvents to obtain quinoline derivatives. Eleven 2-acetylquinolines were synthesized in high yields (85-96%) from symmetrical 1,2-diketone, butan-2,3-dione with o-aminoarylketones in the presence of Eaton's reagent. Subsequently, a novel regioselective solvent free reaction is reported for synthesis of o-aminoarylketones with unsymmetrical 1,2-diketone, pentan-2,3-dione, to yield different 2-propanoylquinolines. Eaton's reagent performs a unique way of this reaction as a powerful desiccant, condensing, cyclizing and dehydrating agent. Among these advantages of Eaton's reagent was found as an inexpensive and easily accessible catalyst for the Friedlander synthesis.
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    Synthesis and biological evaluation of 2,5-diaryl-1,3,4-oxadiazole derivatives as novel Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) inhibitors
    (2021) Meng, Xiang-Dong; Gao, Li-Xin; Wang, Zhi-Jia; Feng, Bo; Zhang, Chun; Satheeshkumar, Rajendran; Li, Jia; Zhu, Yun-Long; Zhou, Yu-Bo; Wang, Wen-Long
    The Src homology-2 domain containing-protein tyrosine phosphatase-2 (SHP2) is a convergent node for oncogenic cell-signaling cascades including the PD-L1/PD-1 pathway. As an oncoprotein as well as a potential immunomodulator, SHP2 has now emerged as an attractive target for novel anti-cancer agents. Although significant progress has been made in identifying chemotypes of SHP2 inhibitors, these specific compounds might not be clinically useful to inhibit frequently encountered mutated SHP2 variants. Consequently, it is highly desirable to develop chemically different SHP2 inhibitors sensitive to SHP2 mutants. This work developed a new type of SHP2 inhibitors with 2,5-diaryl-1,3,4-oxadiazole scaffold. The representative compound 6l exhibited SHP2 inhibitory activity with IC50 of 2.73 +/- 0.20 mu M, showed about 1.56-fold, 5.26-fold, and 7.36-fold selectivity for SHP2 over SHP1, PTP1B and TCPTP respectively. Further investigations confirmed that 6l behaved as mixedtype inhibitor sensitive to leukemia cell TF-1 and inhibited SHP2 mediated cell signaling and proliferation. Molecular dynamics simulation provided more detailed information on the binding modes of compounds and SHP2 protein. These preliminary results could provide a possible opportunity for the development of novel SHP2 inhibitors sensitive to SHP2 mutants with optimal potency and improved pharmacological properties.
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    Synthesis and Cytotoxicity of Novel Indoloquinolines and Benzonaphthyridines from 4-Chloro-2,8-dimethylquinoline and Variety of Hetero Amines
    (2021) Prabha, Kolandaivel; Satheeshkumar, Rajendran; Prasad, K. J. Rajendra
    The synthesis of hetero substituted indoloquinolines and thiophene substituted benzonaphthyridienes from two heterocycles tethered by nitrogen or sulfur intermediates. Further it was cyclized using Pd(OAc)(2) catalyst to yield products, i. e., various heteroindolo quinolines and polyphosphoric acid (PPA) mediated thiophene substituted naphthyridines. All the potential intermediates and their respective final products were screened for anticancer activity against HeLa and K562 cancer cells, and it showed good cytotoxicity against HeLa and K562 cells compared standard Adriamycin (ADR) drugs. Among the newly synthesized compounds, compounds 3 a, 3 b, 4 b and 5 a displayed stronger cytotoxic activity against both HeLa and K562 cells compared standard Adriamycin (ADR) drug. This might be due to the presence of benzothiazole and isoquinoline moieties, which enhanced the cytotoxic activity. Subsequently, compounds 3 c, 3 d, 4 a, 5 b and 7 also showed better cytotoxic activity with IC50 values <19 mu M against HeLa and K562 cells, which was due to the presence of quinoline and thiophene moieties, which enhanced the cytotoxic activity.
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    Synthesis of 2-aminobenzophenone-based Schiff base Pd(II) complexes: Investigation on crystal structure, biological behavior of DNA/protein-binding, molecular docking, andin vitroanticancer activities
    (2020) Satheeshkumar, Rajendran; Wu, Jing; Chandrasekaran, Rajamanickam; Revathi, Kannan; Sparkes, Hazel A.; Wang, Wen-Long
    Two new monobasic bidentate ligands and their Pd(II) complexes have been synthesized and characterized by analytical and spectroscopic methods. The structures of the complexes were confirmed by single-crystal X-ray diffraction. The bimolecular binding of the ligands and complexes has been carried out and described. Interestingly, both the bidentate chelating ligands replaced all the triphenyl arsine and chloride ions from the metal precursor in the formation of new complexes and were found to be approximately square planar. The interaction of the ligands and the complexes with calf thymus DNA and bovine serum albumin was studied by electronic and emission spectroscopy techniques, which suggested an intercalation mode of binding. It is well-known that the viscosity of a DNA solution increases if any compound added binds to it through intercalation because this process lengthens the DNA helix due to the increased separation of the DNA base pairs when the compound slides in between, whereas a partial, nonclassical intercalation could bend (or kink) the DNA helix, which leads to a reduction in length and thereby reducing its viscosity. By contrast, there will be no change in the viscosity when the compounds bind with DNA grooves or by partial intercalation, which was further confirmed by viscosity measurements and molecular docking studies. It has been found that the compounds cleaved supercoiled DNA into nicked DNA without any external agent. Thein vitrocytotoxicity studies of the ligands and complexes against human lung (A549) and breast (MCF7) cancer cell lines showed significant activity for both species.
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    Synthesis of 2-ethoxycarbonylthieno[2,3-b]quinolines in biomass-derived solvent γ-valerolactone and their biological evaluation against protein tyrosine phosphatase 1B
    (2021) Mu, Xu-Yang; Wang, Zhi-Jia; Feng, Bo; Xu, Lei; Gao, Li-Xin; Satheeshkumar, Rajendran; Li, Jia; Zhou, Yu-Bo; Wang, Wen-Long
    A series of 2-ethoxycarbonylthieno[2,3-b]quinolines were synthesized in the bio-derived "green" solvent gamma-valerolactone (GVL) and evaluated for their inhibitory activities against PTP1B, the representative compound 6a displayed an IC50 value of 8.04 +/- 0.71 mu M with 4.34-fold preference over TCPTP. These results provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.
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    Synthesis of Novel Quin[1,2-b]Acridines: In Vitro Cytotoxicity and Molecular Docking Studies
    (2021) Satheeshkumar, Rajendran; Edatt, Lincy; Muthusankar, Aathi; Kumar, V. B. Sameer; Prasad, Karnam Jayarampillai Rajendra
    An attempted synthesis of 5-aryl-6,7-dihydrodibenzo[b,j][1,10]phenanthroline derivatives from 2,3-dihydroacridin-4(1H)-ones with 2-aminocarboxylic acid derivatives in presence of phosphorus oxychloride at 130C yielded a novel class of quin[1,2-b]acridine derivatives. The newly synthesized compounds showed a better cytotoxic activity against HeLa and MCF-7 cell lines during the structure-activity relationship (SAR) studies. To discover with the interactions of these molecules, we carried out molecular docking studies using the human protein kinase CK2 inhibitors. The molecular interaction results provided a number of elegant information for the outlook design of more potent inhibitors.
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    Synthesis, In Vitro Cytotoxicity, and DFT Studies of Novel 2-Amino Substituted Benzonaphthyridines as PDK1 Inhibitors
    (2022) Prabha, Kolandaivel; Satheeshkumar, Rajendran; Nasif, Vesim; Saranya, Jayapalan; Sayin, Koray; Natarajan, Jeyakumar; Chandrasekar, Chinnarasu; Prasad, K. J. Rajendra
    The present work emphasizes the utility of 2,4-dichloro-5-methylbenzo[h][1,6]naphthyridine as starting precursors. The reaction of 2,4-dichloro-5-methylbenzo[h][1,6]naphthyridine with a variety of aliphatic and aromatic amines yielded 2-amino substituted 2,4-dichlorobenzo[h]naphthyridines. All the compounds were examined for their in vitro anticancer activity against six human cancer lines and docked with PDK1 inhibitors. The structure-activity relationship studies are revealed that the compounds holding aminocarbazole moiety and triazole amine moiety improve the activity profile. All the structures of synthesized compounds were optimized at B3LYP-D3/6-31G(d) level in the water. Furthermore, the electronic properties and biological reactivity of the synthesized compounds are explored using computational techniques.
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    Water mediated synthesis of 6-amino-5-cyano-2-oxo-N-(pyridin-2-yl)-4-(p-tolyl)-2H-[1,2′-bipyridine]-3-carboxamide and 6-amino-5-cyano-4-(4-fluorophenyl)-2-oxo-N-(pyridin-2-yl)-2H-[1,2′-bipyridine]-3-carboxamide - An experimental and computational studies with non-linear optical (NLO) and molecular docking analyses
    (2020) Jayarajan, Ramasamy; Satheeshkumar, Rajendran; Kottha, Thirumalaswamy; Subbaramanian, Sabarinathan; Sayin, Koray; Vasuki, Gnanasambandam
    6-Amino-5-cyano-2-oxo-N-(pyridin-2-yl)-4-(p-tolyl)-2H-[1,2'-bipyridine]-3-carboxamide and 6-amino-5cyano-4-(4-fluorophenyl)-2-oxo-N-(pyridin-2-yl)-2H-[1,2'-bipyridine]-3-carboxamide were synthesized through three-component reaction between N-1,N-3-di(pyridin-2-yl)-malonamide, aldehyde and malononitrile in water using triethylamine as a base at room temperature. Synthesized compounds were characterized by using different techniques (FT-IR, NMR and X-ray diffraction). Additionally, the mentioned compounds were investigated by computational chemistry methods. Obtained results were supported with calculated results. Additionally, NLO properties and molecular docking analyses of related compounds were examined in detail. The binding modes of the compounds 4a and 4b were explored with the colchicine binding site of tubulin, from molecular docking studies, remarkable interactions have been observed for 4a and 4b near to the colchicines binding site of tubulin that may contribute to the inhibition of tubulin polymerization and anticancer activity. (c) 2019 Elsevier B.V. All rights reserved.