Browsing by Author "Wang, Wen-Long"

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    Friedlӓnder's synthesis of quinolines as a pivotal step in the development of bioactive heterocyclic derivatives in the current era of medicinal chemistry
    (WILEY, 2022) Rajendran, Satheeshkumar; Sivalingam, Kalaiselvi; Karnam Jayarampillai, Rajendra Prasad; Wang, Wen-Long; Salas Sánchez, Cristián Osvaldo
    In the current scenario of medicinal chemistry, quinoline plays a pivotal role in the design of new heterocyclic compounds with several pharmacological properties, so the search for new synthetic methodologies and their application in drug discovery has been widely studied. So far, many procedures have been performed for the preparation of quinoline scaffolds, among which Friedlander quinoline synthesis plays an important role in obtaining these heterocycles. The Friedlander reaction involves condensation between 2-aminobenzaldehydes and keto-compounds. The quinoline nucleus, once obtained through the Friedlander synthesis, has been extensively modified so that these derivatives can exhibit a large number of biological activities such as anticancer, antimalarial, antimicrobial, antifungal, antituberculosis, and antileishmanial properties. In this work, the focus is on the applicability of the Friedlander reaction in the synthesis of various types of bioactive heterocyclic quinoline compounds, which to date has not been reported in the context of medicinal chemistry. The main part of this review selectively focuses on research from 2010 to date and will present highlights of the Friedlander quinoline synthesis procedures and findings to address biological and pharmacological activities.
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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 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.