Sains Malaysiana 50(3)(2021): 743-751

http://doi.org/10.17576/jsm-2021-5003-16

A Comparative Study of Microwave-Assisted and Conventional Heating Methods of the Synthesis of 1-(Naphthalene-1-Yl)-3-(O, M, P-Tolyl)Thioureas, DFT Analysis, Antibacterial Evaluation and Drug-Likeness Assessment

(Kajian Perbandingan antara Bantuan Mikrogelombang dan Kaedah Pemanasan Konvensional terhadap Sintesis 1-(Naftalena-1-Yl)-3-(O, M, P-Tolil)Tiourea, Analisis DFT, Penilaian Antibakteria dan Kesamaan Ubatan)

SUHAILA SAPARI, EMMA IZZATI ZAKARIAH, NURUL HIDAYAH ABDUL RAZAK, INSYIRAH RAMZAN, MOHD SOFI NUMIN, LEE YOOK HENG, SITI AISHAH HASBULLAH*

Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia

Received: 8 June 2020/Accepted: 27 August 2020

ABSTRACT

New isomers of naphthalene-monothioureas, 3a-3c, were synthesized and characterized by using infrared (IR), ¹H and ¹³ C nuclear magnetic resonance (NMR) and mass spectroscopies (MS). The compounds were obtained from the reaction of o-, m-, p- toluidine with naphthyl isothiocyanate using conventional reflux and microwave-assisted irradiation methods.  Microwave-assisted reaction gave higher yields with reduces the reaction time compared to the conventional heating method. Density Functional Theory (DFT) calculations with 6-31G(d, p) basic set at the B3LYP level is carried out to optimize the structure of isomers and calculate the IR,  ¹H and ¹³ C NMR spectra. The DFT B3LYP calculation of FTIR, ¹H and ¹³C NMR spectra of 3a-3c isomers were in accordance with the experimental data. The calculation of frontier molecular orbitals was also selected to study a relationship as a molecular descriptor in antibacterial activity.  The isomers were screened for their in vitro antibacterial activity by using Staphylococcus aureus bacteria. Inhibition activity was displayed for compound 3c with the value of inhibition zone 7 ± 0.34 mm at a concentration of 10 µg/mL. All compounds appeared to be in agreement with Lipinski’s rule of five assessments as they adhered to most of the rules that can be preliminarily classified as active drug-like.

Keywords: Antibacterial activity; DFT; Lipinski’s rule; microwave irradiation; Thiourea isomers

ABSTRAK

Isomer baru monotiourea-naftalena, 3a-3c telah disintesis dan dicirikan dengan menggunakan spektroskopi infra merah (IM), Spektroskopi Resonans Magnetik Nukleus (RMN) ¹H dan ¹³C dan Spektrometri jisim (SJ). Sebatian ini diperoleh daripada tindak balas antara o-, m-, p- toluidin dengan naftil isotiosianat menggunakan kaedah konvensional refluks dan penyinaran gelombang mikro. Kaedah penyinaran gelombang mikro memberikan hasil yang lebih tinggi pengurangan masa tindak balas berbanding dengan kaedah refluks. Pengiraan Teori Ketumpatan Berfungsi (DFT) dengan set asas 6-31G (d, p) pada aras B3LYP telah dijalankan untuk mengoptimumkan struktur isomer 3a-3c dan mengira spektrum IM, ¹H dan ¹³C RMN. Pengiraan B3LYP spektrum IM, ¹H dan ¹³C RMN isomer 3a-3c adalah bertepatan dengan data uji kaji. Pengiraan orbital molekul frontier juga dipilih untuk mengkaji hubung kait struktur sebatian dalam aktiviti antibakteria. Aktiviti antibakteria dijalankan secara in vitro ke atas semua sebatian dengan menggunakan bakteria Staphylococcus aureus. Aktiviti perencatan dapat dilihat pada sebatian 3c dengan nilai zon perencatan 7 ± 0.34 mm pada kepekatan 10 µg/mL. Kesemua sebatian adalah memenuhi penilaian aturan lima Lipinski's yang boleh dikelaskan berpotensi sebagai ubat aktif.

Kata kunci: DFT; isomer tiourea; mikrogelombang; peraturan Lipinski; sintesis

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*Corresponding author; email: aishah80@ukm.edu.my