International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2021.1.14TaechowisanThongchai SamsawatTipparat JaramornburapongChanjira PhutdhawongWeerachai PhutdhawongWaya S. Phutdhawong 12021171Background and Objective: Geldanamycin (GDM) is an antibiotic isolated from Streptomyces zerumbet W14 that specifically targets and deactivates heat shock protein 90 (Hsp90) to inhibit virus replication. The therapeutic utilization of GDM has been restricted by its low water solubility and severe hepatotoxicity. The aim of the present study was to synthesis the novel geldanamycin derivatives and evaluate their biological properties. Materials and Methods: Five new Dopamine Geldanamycin Hybrids (DGH); compounds 2-6 were synthesized by nucleophilic substitution of GDM (1). Solubility, cytotoxicity, antiviral activity and molecular docking analyses were carried out. Results: The solubility of DGH in water was 0.386-5.464 mM, higher than that of compound 1. These compounds exhibited weak cytotoxic activity against LLC-MK2 and Vero cells, with IC50 values in the range of 104.52-496.31 μg mL1. These compounds (except compound 5) inhibited influenza virus propagation in embryonated chicken eggs at the minimum inhibitory concentration of 6.25 μg mL1. They interacted positively with Hsp90, showing binding free energy (ΔG) of -100.50 to -114.28 kcal mol1, which indicated lower Hsp90 affinity compared with that of geldanamycin (-141.296 kcal mol1) and 17-dimethylamino ethylamino-17-demethoxygeldanamycin (-145.307 kcal mol1), despite being partly bound in the active site (compounds 2, 3 and 6) or outside the active site (compound 4). Conclusion: The study findings revealed, through molecular docking analysis, that the development of DGH improved the pharmacokinetic profiles of solubility, cytotoxicity and antiviral activities. It is, therefore, recommended DGH that is a potential alternative treatment agent for influenza virus infection.]]>Taechowisan, T., W. Puckdee and W.S. Phutdhawong,2019Streptomyces zerumbet, a novel species from Zingiber zerumbet (L.) Smith and isolation of its bioactive compounds.]]>9194219Li, Y.H., P.Z. Tao, Y.Z. Liu and J.D. Jiang, 2004in vitro.]]>48867872Basha, W., R. Kitagawa, M. Uhara, H. Imazu, K. Uechi and J. Tanaka,200516135146Connor, J.H., M.O. McKenzie, G.D. Parks and D.S. Lyles,2007362109119Shan, G.Z., Z.G. Peng, Y.H. Li, D. Li, Y.P. Li, S. Meng, L.Y. Gao, J.D. Jiang and Z.R. Li,201164177182Taechowisan, T., T. Samsawat , W. Puckdee and W.S. Phutdhawong, 2020101221Li, Y.P., G.Z. Shan, Z.G. Peng, J.H. Zhu and S. Meng et al.,201020259268Li, Y.H., Q.N. Lu, H.Q. Wang, P.Z. Tao and J.D. Jiang, 2012in vitro and in vivo.]]>65509512Wang, C., P. Liu, J. Luo, H. Ding and Y. Gao et al.,20172017Supko, J.G., R.L. Hickman, M.R. Grever and L. Malspeis, 199536305315Fukuyo, Y., C.R. Hunt and N. Horikoshi,20102902435Tian, Z.Q., Y. Liu, D. Zhang, Z. Wang and S.D. Dong et al.,20041253175329Wrona, I.E., A. Gozman, T. Taldone, G. Chiosis and J.S. Panek, 20107528202835Modi, S., A. Stopeck, H. Linden, D. Solit and S. Chandarlapaty et al.,20111751325139Kitson, R.R.A., C.H. Chang, R. Xiong, H.E.L. Williams and A.L. Davis et al.,20135307314Lin, Z., R. Peng, Z. Li, Y. Wang and C. Lu, 201536424432Smith, V., E.A. Sausville, R.F. Camalier, H.H. Fiebig and A.M. Burger,2005in vitro: Effects on Hsp90 and client proteins in melanoma models.]]>56126137Bhatt-Mehta, V. and M.C. Nahata,19899303314Chase, G., T. Deng, E. Fodor, B.W. Leung, D. Mayer, M. Schwemmle and G. Brownlee,2008377431439Taechowisan, T., K. Dumpin and W.S. Phutdhawong,201812713Brauer, R. and P. Chen,20152015Banerji, U., I. Judson and P. Workman,20033385390Stebbins, C.E., A.A. Russo, C. Schneider, N. Rosen, F.U. Hartl and N.P. Pavletich,199789239250Sarkar, C., B. Basu, D. Chakroborty, P.S. Dasgupta and S. Basu,201024525528Torres-Rosas, R., G. Yehia, G. Peña, P. Mishra and M.D.R. Thompson-Bonilla et al.,201420291295Chavan, S.S. and K.J. Tracey,201420239241Simplício, A.L., J.M. Clancy and J.F. Gilmer,200813519547Atlas, D.,201622461467El-Naggar, M., A.N. El-Shorbagi, D.H. Elnaggar, A.E.G.E. Amr, M.A. Al-Omar and E.A. Elsayed,2018201819Ramesh, M., P. Makam, C. Voshavar, H. Khare, K. Rajasekhar, S. Ramakumar and T. Govindaraju,20181676827692