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Linear diarylheptanoids as potential anticancer therapeutics: synthesis, biological evaluation, and structure–activity relationship studies

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Abstract

In efforts to develop effective anticancer therapeutics with greater selectivity toward cancerous cell and reduced side-effects, such as emetic effects due to detrimental action of the drug toward the intestinal flora, a series of linear diarylheptanoids (LDHs) were designed and synthesized in 7 steps with good-to-moderate yields. All synthesized compounds were evaluated for their antibacterial, antiproliferative, and topoisomerase-I and -IIα inhibitory activity. Overall, all compounds showed little to no activity against the bacterial strains tested. Most of the synthesized compounds showed good antiproliferative activity against human breast cancer cell lines (T47D); specifically, the IC50 values of compounds 6a, 6d, 7j, and 7e were 0.09, 0.64, 0.67, and 0.99 μM, respectively. Among the tested compounds, 7b inhibited topo-I by 9.3% (camptothecin 68.8%), 7e and 7h inhibited topo-IIα by 38.4 and 47.4% (etoposide 76.9%), respectively, at the concentration of 100 μM. These results suggest that a set of promising anticancer agents can be obtained by reducing inhibitory actions on different microbes to provide enhanced selectivity against cancerous cells.

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Acknowledgements

This work was supported by the NSTIP Strategic Technologies Program (Number 12-MED-2439-02) in the Kingdom of Saudi Arabia.

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  1. A. F. M. Motiur Rahman and Yang Lu are equally contributed.

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia

    A. F. M. Motiur Rahman, Wencui Yin & Adnan A. Kadi

  2. College of Pharmacy, Yeungnam University, Gyeongsan, 38541, South Korea

    Yang Lu, Hyochang Cha & Yurngdong Jahng

  3. College of Pharmacy, Ewha Womans University, Seoul, 03760, Republic of Korea

    Hwa-Jong Lee, Hyunji Jo & Youngjoo Kwon

  4. Department of Chemistry, Jagannath University, Dhaka, 1100, Bangladesh

    Mohammad Sayed Alam

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Motiur Rahman, A.F.M., Lu, Y., Lee, HJ. et al. Linear diarylheptanoids as potential anticancer therapeutics: synthesis, biological evaluation, and structure–activity relationship studies. Arch. Pharm. Res. 41, 1131–1148 (2018). https://doi.org/10.1007/s12272-018-1004-8

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