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Volume 13
Issue 11
10.3390/ph13110390
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Article

Synthesis of New 1, 3, 4-Oxadiazole-Incorporated 1, 2, 3-Triazole Moieties as Potential Anticancer Agents Targeting Thymidylate Synthase and Their Docking Studies

by
Mohammad Mahboob Alam
1,
Abdulraheem SA Almalki
2,
Thikryat Neamatallah
3,†,
Nada M. Ali
1,
Azizah M. Malebari
4 and
Syed Nazreen
1,*,†
1
Department of Chemistry, Faculty of Science, Albaha University, Albaha-1988, Saudi Arabia
2
Department of Chemistry, Faculty of Science, Taif University, Taif-21974, Saudi Arabia
3
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
4
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceuticals 2020, 13(11), 390; https://doi.org/10.3390/ph13110390
Submission received: 22 October 2020 / Revised: 9 November 2020 / Accepted: 12 November 2020 / Published: 14 November 2020
(This article belongs to the Special Issue Anticancer Drugs 2021)
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Abstract

Thymidylate synthase (TS) has emerged as a hot spot in cancer treatment, as it is directly involved in DNA synthesis. In the present article, nine hybrids containing 1,2,3-triazole and 1,3,4-oxadiazole moieties (6–14) were synthesized and evaluated for anticancer and in vitro thymidylate synthase activities. According to in silico pharmacokinetic studies, the synthesized hybrids exhibited good drug likeness properties and bioavailability. The cytotoxicity results indicated that compounds 12 and 13 exhibited remarkable inhibition on the tested Michigan Cancer Foundation (MCF-7) and Human colorectal Carcinoma (HCT-116) cell lines. Compound 12 showed four-fold inhibition to a standard drug, 5-fluoruracil, and comparable inhibition to tamoxifen, whereas compound 13 exerted five-fold activity of tamoxifen and 24-fold activity of 5-fluorouracil for MCF-7 cells. Compounds 12 and 13 inhibited thymidylate synthase enzyme, with an half maximal inhibitory concentration, IC50 of 2.52 µM and 4.38 µM, while a standard drug, pemetrexed, showed IC50 = 6.75 µM. The molecular docking data of compounds 12 and 13 were found to be in support of biological activities data. In conclusion, hybrids (12 and 13) may inhibit thymidylate synthase enzyme, which could play a significant role as a chemotherapeutic agent.
Keywords: thymidylate synthase; cytotoxicity; 1,2,3-triazole; 1,3,4-oxadiazole; 5-fluoruracil; pemetrexed; docking thymidylate synthase; cytotoxicity; 1,2,3-triazole; 1,3,4-oxadiazole; 5-fluoruracil; pemetrexed; docking
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MDPI and ACS Style

Alam, M.M.; Almalki, A.S.; Neamatallah, T.; Ali, N.M.; Malebari, A.M.; Nazreen, S. Synthesis of New 1, 3, 4-Oxadiazole-Incorporated 1, 2, 3-Triazole Moieties as Potential Anticancer Agents Targeting Thymidylate Synthase and Their Docking Studies. Pharmaceuticals 2020, 13, 390. https://doi.org/10.3390/ph13110390

AMA Style

Alam MM, Almalki AS, Neamatallah T, Ali NM, Malebari AM, Nazreen S. Synthesis of New 1, 3, 4-Oxadiazole-Incorporated 1, 2, 3-Triazole Moieties as Potential Anticancer Agents Targeting Thymidylate Synthase and Their Docking Studies. Pharmaceuticals. 2020; 13(11):390. https://doi.org/10.3390/ph13110390

Chicago/Turabian Style

Alam, Mohammad Mahboob, Abdulraheem SA Almalki, Thikryat Neamatallah, Nada M. Ali, Azizah M. Malebari, and Syed Nazreen. 2020. "Synthesis of New 1, 3, 4-Oxadiazole-Incorporated 1, 2, 3-Triazole Moieties as Potential Anticancer Agents Targeting Thymidylate Synthase and Their Docking Studies" Pharmaceuticals 13, no. 11: 390. https://doi.org/10.3390/ph13110390

APA Style

Alam, M. M., Almalki, A. S., Neamatallah, T., Ali, N. M., Malebari, A. M., & Nazreen, S. (2020). Synthesis of New 1, 3, 4-Oxadiazole-Incorporated 1, 2, 3-Triazole Moieties as Potential Anticancer Agents Targeting Thymidylate Synthase and Their Docking Studies. Pharmaceuticals, 13(11), 390. https://doi.org/10.3390/ph13110390

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