Design, synthesis, and evaluation of novel ursolic acid derivatives as HIF-1α inhibitors with anticancer potential

Chi, Ke-Qiang; Wei, Zhi‐Yu; Wang, Ke-Si; Wu, Jie; Chen, Weiqiang; Jin, Xuejun; Piao, Hu‐Ri

doi:10.1016/j.bioorg.2017.09.013

Cited by 31 publications

(17 citation statements)

References 48 publications

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“…Compound 18 (Figure 10) demonstrated excellent activity inhibiting the expression of HIF-1a, with IC 50 ¼ 38.1 mM, possessing a lower appreciable cytotoxic activity (IC 50 > 100 mmol/L) than that of UA (IC 50 ¼ 23.8 mmol/L). SAR indicating that the triazolone moiety was favourable for HIF-1a inhibition in the UA derivatives, and introducing a piperazine ring to the oxadiazole structure can also enhance the biological activity of the compounds 45 . In 2016, Tian et al reported that the introduction of a piperazine moiety at the C-28 position of oleanolic acid (OA) and UA demonstrated a superior growth inhibition against MCF-7 cancer cells than the lead compounds or positive control gefitinib, including derivatives 19 (Figure 10), 21 (Figure 10), 23 (Figure 11) and 24 (Figure 11), with IC 50 values of 40.27 ± 4.88 mM, 56.85 ± 4.88 mM, 12.1 mM, and 14.2 mM, respectively 46,47 .…”

Section: Biological Effects Of Natural Products Containing the Piperazinyl Moietymentioning

confidence: 99%

Piperazine skeleton in the structural modification of natural products: a review

Zhang

Guo

Deng

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Piperazine moiety is a cyclic molecule containing two nitrogen atoms in positions 1 and 4, as well as four carbon atoms. Piperazine is one of the most sought heterocyclics for the development of new drug candidates with a wide range of applications. Over 100 molecules with a broad range of bioactivities, including antitumor, antibacterial, anti-inflammatory, antioxidant, and other activities, were reviewed. This article reviewed investigations regarding piperazine groups for the modification of natural product derivatives in the last decade, highlighting parameters that affect their biological activity.

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Section: Biological Effects Of Natural Products Containing the Piperazinyl Moietymentioning

confidence: 99%

Piperazine skeleton in the structural modification of natural products: a review

Zhang

Guo

Deng

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…These results indicated that the simple esterification of the UA carboxyl moiety can result in a significantly enhanced inhibitory effect on HIF-1α activity and decreased toxicity. The mechanism of action suggested that 13b can also suppress cell proliferation and block cell cycle progression in the G1 phase ( Scheme 3 ) [ 156 ].…”

Section: Chemistry Of Uamentioning

confidence: 99%

Ursolic Acid-Based Derivatives as Potential Anti-Cancer Agents: An Update

Khwaza

Oyedeji

Aderibigbe

2020

IJMS

115

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Ursolic acid is a pharmacologically active pentacyclic triterpenoid derived from medicinal plants, fruit, and vegetables. The pharmacological activities of ursolic acid have been extensively studied over the past few years and various reports have revealed that ursolic acid has multiple biological activities, which include anti-inflammatory, antioxidant, anti-cancer, etc. In terms of cancer treatment, ursolic acid interacts with a number of molecular targets that play an essential role in many cell signaling pathways. It suppresses transformation, inhibits proliferation, and induces apoptosis of tumor cells. Although ursolic acid has many benefits, its therapeutic applications in clinical medicine are limited by its poor bioavailability and absorption. To overcome such disadvantages, researchers around the globe have designed and developed synthetic ursolic acid derivatives with enhanced therapeutic effects by structurally modifying the parent skeleton of ursolic acid. These structurally modified compounds display enhanced therapeutic effects when compared to ursolic acid. This present review summarizes various synthesized derivatives of ursolic acid with anti-cancer activity which were reported from 2015 to date.

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“…Ursolic acid antitumor activity has long been recognized, probably being responsible for the anticancer properties of some plants used in Chinese traditional medicine. The antiangiogenic activity of ursolic acid was evidenced by the early observation that it interfered several steps of the angiogenic process in vitro [74], later being characterized as an inhibitor of multiple signaling pathways controlling cancer growth and angiogenesis [75], including that of HIF-1α [76]. In addition, studies of the ursolic acid biodisponibility after oral administration in mice, and the toxicity, pharmacokinetic, and pharmacodynamics of liposomal ursolic acid in humans have shown promising results, supporting its use in cancer chemoprevention [77].…”

Section: Olive Oil As a Source Of Antiangiogenic Moleculesmentioning

confidence: 99%

The Mediterranean Diet, a Rich Source of Angiopreventive Compounds in Cancer

et al. 2019

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Diet-based chemoprevention of cancer has emerged as an interesting approach to evade the disease or even target its early phases, reducing its incidence or slowing down tumor progression. In its basis in the essential role of angiogenesis for tumor growth and metastasis, angioprevention proposes the use of inhibitors of angiogenesis in cancer prevention. The anti-angiogenic potential exhibited by many natural compounds contained in many Mediterranean diet constituents makes this dietary pattern especially interesting as a source of chemopreventive agents, defined within the angioprevention strategy. In this review, we focus on natural bioactive compounds derived from the main foods included in the Mediterranean diet that display anti-angiogenic activity, as well as their possible use as angiopreventive agents.

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Design, synthesis, and evaluation of novel ursolic acid derivatives as HIF-1α inhibitors with anticancer potential

Cited by 31 publications

References 48 publications

Piperazine skeleton in the structural modification of natural products: a review

Piperazine skeleton in the structural modification of natural products: a review

Ursolic Acid-Based Derivatives as Potential Anti-Cancer Agents: An Update

The Mediterranean Diet, a Rich Source of Angiopreventive Compounds in Cancer

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