Vol.4 , No. 3, Publication Date: Jan. 30, 2019, Page: 32-38
[1] | Ahmed Ali Al–Hazmi, Department of Chemistry, Ibb University, Ibb City, Yemen. |
[2] | Waddhaah Mohammed Alasbahy, Department of Chemistry, Ibb University, Ibb City, Yemen. |
[3] | Labeeb Mohammed Shaif, Department of Chemistry, Ibb University, Ibb City, Yemen. |
[4] | Gaber Al–Gaber, Department of Chemistry, Ibb University, Ibb City, Yemen. |
[5] | Manal Shamsi, Department of Chemistry, Ibb University, Ibb City, Yemen. |
A new series of 6–phenyl pyridine derivatives were synthesized by using (2E)–1–phenyl–3–(thiophen–2–yl) prop–2–en–1–one (1) reacted with 2–cyanoethane–thioamide (2) to afford the corresponding 6–phenyl–4–(thiophen–2–yl) 2–thioxo–1,2–dihydropyridine–3–carbonitriles (6). The synthetic potentiality of compound 6 was investigated in the present study via their reactions with active–hydrogen containing compounds ethyl chloroacetate 8 aiming to synthesize 4–(thiophen–2–yl)–6–phenylthieno [2, 3–b] pyridin–3–amines 10 via ethyl {[3–cyano–6–phenyl–4–(thiophen–2–yl) pyridin–2–yl] sulfanyl}acetate 9. Compounds 9 and10 reacted with hydrazine hydrate in EtOH to afford the corresponding 3–amino–6–phenyl–4–(thiophen–2–yl) thieno [2, 3–b] pyridine–2–carbohydrazide 11. Structures of the title compounds were characterized by UV, IR, 1H/13C-NMR and mass spectrometric methods as well as that of elemental analyses. The compound 11 have been screened for anti–bacterial activity and molecular docking studies. UV, IR, 1H/13C-NMR and mass spectral data, the assigned structure were established. The synthesized compound 11 showed potent antimicrobial activity against the selected strains of Gram-positive Gram-negative bacteria. Furthermore, The molecular docking technique was utilized to ascertain the mechanism and mode of action towards the molecular target cyclin–dependent kinase (CDK) inhibitor protein indicating that compound 11 has been exhibit inhibitory activity against CDK inhibitors via H–bonds and electrostatic interactions. The main purpose of this paper is synthesis of new 6–phenyl pyridine derivatives to provide an insight into its biological activities which contain the carbohydrazide moiety. The synthesized of new 6–phenyl pyridine derivatives which contain the carbohydrazide moieties have shown promising antimicrobial activities and inhibition activity against cyclin–dependent kinase (CDK) protein.
Keywords
6–Phenyl Pyridine, Antimicrobial, Molecular Docking
Reference
[01] | Radha K, Chanmi P, Kyu–Yeon J, Tara MK, Eung–Seok L, Youngjoo K., J. Med. Chem. 90 (2015) 360. |
[02] | Gopal D. V., Srinivas N, Srinivas B, Kulkarnia S. J., Subrahmanyam M., Green Chem., 3 (2001) 65. |
[03] | Mamolo M. G., Falagiani V., Zampieri D., Vio L., Banfi E., Il Farmaco. 55 (2000) 590. |
[04] | Vane J. R., J. Rheumatol. 35 (1996) 1. |
[05] | Kurumbail R. G. A., Stevens M., Gierse J. K., McDonald J. J., Nature 384 (1996) 644. |
[06] | Dempcy R. O., and Skibo E. B., Bioorg. Med. Chem. Lett. 1 (1993) 39. |
[07] | Mustard D., Ritchie D. W., Prot. Struct. Funct. Bioinf. 60: (2005) 269. |
[08] | Wang S., Griffiths G., Midgley C., Meades C, O’Boyle J., Gibson D., Wood G., Grabarek J., Cooper M, Mezna M., Proc. Am. Assoc. Cancer Res. 46 (2005) 110. |
[09] | Wang S., Meades C., Wood G., Osnowski A., Anderson S., Yuill R., Thomas M., Mezna M., Jackson W., Midgley C., J. Med. Chem. 47 (2004) 1662. |
[10] | Baumli, S., Lolli, G., Lowe, E. D., Troiani, S., Rusconi, L., Bullock, A. N., Debreczeni, J. E., Knapp, S., and Johnson, L. N., EMBO J. 27 (2008) 1907. |