PRESS RELEASE – Pterocarpanquinones and carbapterocarpans with anti-tumor activity against MDR leukemias

The article by Dr. Vivian M. Rumjanek et al. is published in Anti-Cancer Agents in Medicinal Chemistry, 2018

Careful thinking must be put since the very first days of the design of a new drug candidate to consider variables such as cost-effectiveness, novelty, side effects and the peculiarity of the disease to be treated. Cancer, as a multifactorial sum of diseases, present challenges since its high mutational background often grants tumor cells varying mechanisms to sustain cellular proliferation. Our group, consisting on researchers with different backgrounds as well, resorted to nature to find chemical groups that would present good in vivo tolerance with possibilities for further development. Pterocarpans, secondary metabolites derived mainly from isoflavonoids of the Papilionoideae subfamily of the Leguminosae plant family, served this purpose. They possess anti-inflammatory and antineoplastic properties along with a highly ‘moddable’ scaffold comprising phenolic rings. Addition of two prime pharmacophores such as naphthoquinones and sulfonamides added new mechanisms of antineoplastic action, since the first display prooxidant activity and the latter are described to inhibit tubulin polymerization and tyrosine kinases. Considering this, the resulting molecules LQB-118 and LQB-223 would likely induce toxicity to a variety of tumor cells.

Multidrug resistance (MDR), the major hurdle to a successful therapy outcome, would present additional challenges. Diverse mechanisms act in MDR to evade drug-induced apoptosis: changes in cell cycle and metabolic adaptation to the insult exerted by chemotherapeutics, upregulation of protective responses such as resistance to oxidative stress and antiapoptotic proteins (IAPs) and increase in the activity of efflux transporter proteins. These adaptations are dynamic and highly variable among tumor subtypes, in a way that drug design projects often show its shortcomings when MDR is considered. Our results indicated otherwise; in leukemic cells, inhibition induced by the hybrid pterocarpanquinone LQB-118 did not seem to associate with blockade on a particular phase of the cell cycle. On solid tumors, however, an increase in the G2/M phase was observed. On leukemias, suppression of the master cell cycle regulator FoxM1 produced changes in diverse phases of the cell cycle according to the cell subtype; on prostate cancer downregulation of cyclins B1 and D1 were present. Regarding protective responses, LQB-118 was able to overcome two of the most effective in dealing with cellular stress, increases in glutathione to counter oxidative damage and upregulation of survivin and XIAP to evade apoptosis. This profile would likely be associated to inhibition of a broad, upstream transcriptional regulator, and NF?B emerged as the cellular target of LQB-118. In addition, the effect of this compound was increased when autophagy was promoted with rapamycin, and no changes manifested when this pathway was inhibited with chloroquine. Downstream apoptotic responses were observed accordingly, such as calcium leakage from the endoplasmic reticulum, mitochondrial outer membrane depolarization, caspases’ and PARP activation, and DNA fragmentation.

It became clear that LQB-118 was able to ‘tweak’ its mode of action and exert toxicity to different tumor cells. The multiple pathways affected are the reflection of the way the particular cell tries to circumvent the insult produced by this drug. This could partially be explained by the hybrid nature of LQB-118, in which both its pterocarpan and quinone scaffolds act in synergy for the bioactivation of this drug, producing oxidative and/or alkylating damage depending on the intrinsic biological feature of the tumor subtype. This would be nothing out of ordinary if this resulted in unacceptable toxicity to healthy organisms. Our group performed extensive studies on normal mice with diverse immunologic backgrounds, and this compound was able to reach its final targets in vivo, reducing tumor growth sparing normal cells. A similar outcome was observed on both healthy and neoplastic cells from leukemic patients at the National Cancer Institute of Brazil. Our compounds were designed to be effective in cells with MDR phenotype; as such, it was important to evaluate their efficacy on cells overexpressing ABC proteins. Given their isoflavonoid origin, LQB-118 was able to circumvent high levels of ABCB1 protein expression and functional activity, a profile that was maintained on LQB-223, the carba-derivative that was designed not to repeat the same molecular mechanisms displayed by LQB-118 (thus avoiding the non-innovative ‘me-too’ molecules). LQB-223 acted regardless of both ABCB1 and ABCC1 overexpression in leukemias as well as breast cancer cells, being of broader scope than LQB-118. Owing to its sulfonamide moiety, LQB-223 was demonstrated to bind to the minor groove of DNA, and recent yet unpublished results suggest DNA topoisomerases and ?-tubulin as targets of this carbapterocarpan, expanding its use.

Tracing back to the origins of the compounds, the diverse natures of our research group and the variety of prime chemical groups employed resulted in compounds with a myriad of mechanisms, adaptable to diverse phenotypes of drug resistance. The radical innovation applied to a prototypical chemical structure propose LQB-118 and LQB-223 as antineoplastic drug candidates directed to drug-resistant neoplasias, with good selectivity and interesting mechanistic features.

For more information, please visit:


Current Molecular Medicine 17, Issue 8

Current Medicinal Chemistry 25, Issue 7

Anti-Cancer Agents in Medicinal Chemistry 18, Issue 1

Mini-Reviews in Medicinal Chemistry 18, Issue 6

Current Medicinal Chemistry 25, Issue 8

Current Drug Targets 19, Issue 5 



EDITOR’S CHOICE – Novel Findings of Anti-cancer Property of Propofol – Anti-Cancer Agents in Medicinal Chemistry

Journal: Anti-Cancer Agents in Medicinal Chemistry

Author(s): Jiaqiang Wang, Chien-shan Cheng, Yan Lu, Xiaowei Ding, Minmin Zhu, Changhong Miao*, Jiawei Chen*

Graphical Abstract:


Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia.

Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear.

Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol’s malignance-modulating properties and the potential molecular mechanisms.

Read more here:


Press Release – The clinical and experimental research on the treatment of endometriosis with thiostrepton

This article by Dr. Ping Jin et al. is published in Anti-Cancer Agents in Medicinal Chemistry, Volume 18, 2018

Forkhead Box M1 (FOXM1), which known as Trident, HNF-3, HFH-11, MPP2, and Win, is a transcriptional factor that plays an important role in cell proliferation, differentiation, and transformation. As one of the early up-regulated proteins in cancerogenesis, FOXM1 is frequently activated in tumors. This research studied the expression and the possible mechanism of FOXM1 and evaluated the effects of thiostrepton in an endometriotic rat model.

The research concluded two part. On the one hand, we constructed the rats model of endometriosis. Observed the expression of FOXM1 in endometriosis tissues. Explored the possible mechanism of FOXM1 action, like EKR?FOXM1 and MMP9 Signaling Pathway. Fifty female Wistar rats were surgically induced with endometriosis. After 4 weeks of observation, twenty and thirty rats were randomly allocated to an ovariectomized (OVX) group and a treatment group, respectively. The OVX group was ovariectomized and randomly divided into an OVX-estrogen group and a control (OVX -oil) group. All rats were allowed a resting period of 3 days prior to any operation. The rats in the estrogen group were given estradiol (20 μg/kg, 0.1 ml /d), while the control group was treated with an equivalent amount of sesame oil. Every group was injected with subcutaneous injection for 7 days. Our results showed that FOXM1 is enrich in nucleus of an ectopic endometrium when compared with an eutopic uterus. Furthermore, we found that an ERK/FOXM1/matrix metalloproteinase-9 (MMP9) signaling pathway might result in the establishment and development of endometriosis.

On the other hand, thiostrepton is a small-molecule inhibitor of the transcription factor FOXM1. We evaluated the effects of thiostrepton in an endometriotic rat model. The treatment group was randomly divided into three groups to receive the following: TST at 150 mg/kg, ip.; TST at 250 mg/kg, ip.; or sterile normal saline, ip. The groups received these dosages every 2 days for 2 weeks. Lesion growth, histological examination, and protein expression were subsequently analyzed using caliper measurement, histology, immunostaining, and Western blot after each rat received an injection in its own group. Our results showed that a thiostrepton concentration dependently reduced the expression of FOXM1, MMP9 and Bcl-2 in endometriotic lesions of the treated rats. Statistical significance was accepted for a value of P < 0.05.

In conclusion, we postulate that thiostrepton could inhibit the endometriotic lesions, at least in part, by decreasing the FOXM1 expression and exerting a pro-apoptotic effect. We reported for the first time that FOXM1 expresses in experimental endometriosis rat and thiostrepton may also be suitable for the administration of endometriosis by inhibiting the growth of endometriotic implants.

For more information, please visit:

OPEN ACCESS ARTICLE – Regulation of Apoptosis by SYB in HepG2 Liver Cancer Cells is Mediated by the P53/Caspase 9 Axis – Anti-Cancer Agents in Medicinal Chemistry

Journal: Anti-Cancer Agents in Medicinal Chemistry

Author(s): Sharula, Zhongjun Wu*

Graphical Abstract:



Objective: To explore the function of miR-34a in promotion of apoptosis by SYB.

Methods: In this study, the most effective concentration of SYB was determined by measuring cell proliferation. Relative miR-34a mRNA levels were detected by quantitative RT-PCR. Apoptosis was assessed using Annexin- V/PI assays, whereas protein levels of p53, caspase 3, caspase 9, caspase 8 and Bcl2 were evaluated by western blotting.

Results: Minimum HepG2 cell growth was observed after 36h of exposure to 150 nmol/L SYB. miR-34a expression was highest 40min after the addition of SYB. SYB slightly decreased the abundance of Bcl-2, but increased the abundance of p53, caspase 3, caspase 9 and caspase 8. SYB failed to alter miR-34a expression when p53 was inhibited. Bcl-2 abundance remained low over time, whereas the abundance of caspase 3, caspase 9 and caspase 8 gradually increased. Inhibition of p53 promoted HepG2 cell growth in comparison with that of the control group. miR-34a was silenced to assess the role of miR-34a in the inhibitory effect of SYB on HepG2 cell growth. When p53 was silenced, protein abundance of Bcl2, caspase 3, caspase 8 and caspase 9 remained unchanged following the addition of SYB; moreover, HepG2 cell growth was increased.
Conlusion: SYB represents a promising therapeutic approach for liver cancer patients.



Medicinal Chemistry Volume 14, Issue 2

Clinical Immunology, Endocrine & Metabolic Drugs Volume 4, Issue 1

Anti-Cancer Agents in Medicinal Chemistry Volume 17, Issue 14

Letters in Organic Chemistry Volume 15, Issue 3

Current Molecular Medicine Volume 17, Issue 6

Protein & Peptide Letters Volume 24, Issue 12



Current Psychiatry Reviews13-3

Anti-Cancer Agents in Medicinal Chemistry 17-11

Current Medicinal Chemistry 24 -36

Current Organic Chemistry 21-23

Current Organic Synthesis 14 -7

Current Pharmaceutical Design 23-30

Current Drug Targets  18-16

Current Medicinal Chemistry 24 -37

Current Genomics 19 -1

Current Pharmaceutical Design 23 -31



Current Genomics  18-6

Letters in Organic Chemistry 14-9

Anti-Cancer Agents in Medicinal Chemistry 17-10

Recent Patents on Anti-Infective Drug Discovery 12-1

Current Organic Chemistry 21-18

Letters in Drug Design & Discovery 14-11

Current Pharmaceutical Design 23-26



Wishing A Very Happy Birthday to Dr. Michelle Prudhomme!

Dr. Michelle Prudhomme

Dr. Michelle Prudhomme

EDITOR-IN-CHIEF: Anti-Cancer Agents in Medicinal Chemistry

Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

Highlighted Article – Doxycycline as Potential Anti-Cancer Agent – Anti-Cancer Agents in Medicinal Chemistry

acamc- Articles_17-14-Khalid O. Alfarouk