Next Article in Journal
Inhibition of CYP2B6 by Medicinal Plant Extracts: Implication for Use of Efavirenz and Nevirapine-Based Highly Active Anti-Retroviral Therapy (HAART) in Resource-Limited Settings
Previous Article in Journal
Constructing a MoS2 QDs/CdS Core/Shell Flowerlike Nanosphere Hierarchical Heterostructure for the Enhanced Stability and Photocatalytic Activity
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Molecules 2016, 21(2), 214;

Synthesis, Molecular Structure Optimization, and Cytotoxicity Assay of a Novel 2-Acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene

Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
King Abdulaziz City for Science and Technology, P.O. Box 6086, Riyadh 11442, Saudi Arabia
Department of Chemistry, Rabigh College of Science and Art, King Abdulaziz University, P. O. Box 344, Rabigh 21911, Saudi Arabia
Department of Chemistry, Faculty of Science, Alexandria University, P. O. Box 426, Ibrahimia, 21321 Alexandria, Egypt
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
Lab of Chemical Material, Faculty of Sciences, University Mohammed Premier, Oujda 60000, Morocco
Department of Chemistry, The University of Jordan, Amman 11942, Jordan
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 8 January 2016 / Revised: 4 February 2016 / Accepted: 4 February 2016 / Published: 15 February 2016
(This article belongs to the Section Organic Chemistry)
Full-Text   |   PDF [1834 KB, uploaded 19 February 2016]   |  


A novel thiophene-containing compound, 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene (4) was synthesized by reaction of malononitrile with CS2 in the presence of K2CO3 under reflux in DMF and the subsequent reaction with chloroacetone followed by cyclization. This compound has been characterized by means of FT-IR, 1H-NMR, 13C-NMR, and mass spectrometry as well as elemental analysis. In addition, the molecular structures of compound 4 was determined by X-ray crystallography. The geometry of the molecule is stabilized by an intramolecular interaction between N1–H1···O1 to form S6 graf set ring motif. In the crystal, molecules are linked via N1–H2···O1 and C7–H7A···N2 interactions to form a three-dimensional network. Molecular structure and other spectroscopic properties of compound 4 were calculated using DFT B3LYP/6-31G (d,p) method. Results revealed a good agreement between the optimized geometric parameters and the observed X-ray structure. Furthermore, and by employing the natural bond orbital (NBO) method, the intramolecular charge transfer (ICT) interactions along with natural atomic charges at different sites, were calculated; results indicated strong n→π* ICT from LP(1)N5→BD*(2)C15-C16 (63.23 kcal/mol). In addition, the stabilization energy E(2) of the LP(2)O3→ BD*(1)N5-H6 ICT (6.63 kcal/mol) indicated the presence of intramolecular N-H···OH bonding. Similarly, calculations of the electronic spectra of compound 4 using, TD-DFT revealed a good agreement with the experimental data. Finally, compound 4 was evaluated for its in vitro cytotoxic effect against PC-3 and HeLa cell lines, as an anticancer agent, and found to be nontoxic. View Full-Text
Keywords: 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene; X-ray diffraction; DFT; molecular structure; cytotoxicity 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene; X-ray diffraction; DFT; molecular structure; cytotoxicity

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Mabkhot, Y.N.; Aldawsari, F.D.; Al-Showiman, S.S.; Barakat, A.; Soliman, S.M.; Choudhary, M.I.; Yousuf, S.; Ben Hadda, T.; Mubarak, M.S. Synthesis, Molecular Structure Optimization, and Cytotoxicity Assay of a Novel 2-Acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene. Molecules 2016, 21, 214.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top