Curcumin inspired synthesis of unsymmetrical diarylpentanoids with highly potent anti-parasitic activities: in silico studies and DFT-based stereochemical calculation

Din, Zia Ud; Santos, Alef dos; Almeida‐Trapp, Marilia; Lazarin‐Bidóia, Danielle; Garcia, Francielle P.; Peron, Francieli; Nakamura, Celso Vataru; Rodrigues‐Filho, Edson

doi:10.1039/c5md00599j

Cited by 8 publications

(7 citation statements)

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“…Diarylpentanoids comprise a class of natural products and their synthetic analogues, structure related with chalcones, possessing two aromatic rings connected by a five-carbon bridge. These compounds have gained increasing interest over the last few decades due to a wide variety of biological activities, including antioxidant [ 19 ], anti-inflammatory [ 20 ], antitumor [ 21 ], antidiabetic [ 22 ], antibacterial [ 23 ], antiparasitic [ 24 ], and antihyperuricemic [ 25 ]. In addition, diarylpentanoids have also been described for their ability to interfere with several proteins, namely enzymes [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ] (oxidoreductases, glycosidases, phosphatases, cholinesterases, and carbonic anhydrase II), and channel proteins (P-gp, BCRP, MRP1, MRP5, TRPA1, TRPM8, and TRPV1).…”

Section: Introductionmentioning

confidence: 99%

BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

et al. 2021

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Previously, we reported the in vitro growth inhibitory effect of diarylpentanoid BP-M345 on human cancer cells. Nevertheless, at that time, the cellular mechanism through which BP-M345 exerts its growth inhibitory effect remained to be explored. In the present work, we report its mechanism of action on cancer cells. The compound exhibits a potent tumor growth inhibitory activity with high selectivity index. Mechanistically, it induces perturbation of the spindles through microtubule instability. As a consequence, treated cells exhibit irreversible defects in chromosome congression during mitosis, which induce a prolonged spindle assembly checkpoint-dependent mitotic arrest, followed by massive apoptosis, as revealed by live cell imaging. Collectively, the results indicate that the diarylpentanoid BP-M345 exerts its antiproliferative activity by inhibiting mitosis through microtubule perturbation and causing cancer cell death, thereby highlighting its potential as antitumor agent.

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Section: Introductionmentioning

confidence: 99%

BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

et al. 2021

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“…Monocarbonyl curcuminoids are also among those functionalities that could be generated by the simple condensation reaction of aliphatic ketones and aromatic aldehydes. A curcuminoid is a linear diarylpentanoid having one carbonyl or a linear diarylheptanoid having two carbonyl groups . Traditionally, monocarbonyl curcuminoids have been investigated for their assembly and molecular possessions .…”

Section: Introductionmentioning

confidence: 99%

Exploration of Noncovalent Interactions, Chemical Reactivity, and Nonlinear Optical Properties of Piperidone Derivatives: A Concise Theoretical Approach

et al. 2020

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The organic compounds with a π-bond system lead to electric charge delocalization which enables them to reveal fascinating nonlinear optical properties. Mono-carbonyl curcuminoids also have an appealing skeleton from the conjugation view point. Interesting chemical structures of the 3,5-bis(arylidene)-Nbenzenesulfonyl-4-piperidone derivatives motivated us to perform density functional theory (DFT)-based studies. Therefore, computations using the B3LYP/6-311G(d,p) functional of DFT were executed to explore geometric parameters, highest occupied molecular orbital (HOMO)−lowest unoccupied molecular orbital (LUMO) energies, and natural bond orbital (NBO) analyses. Moreover, three different functionals such as HF, B3LYP, and M06 with the 6-311G(d,p) basis set were used to investigate the average polarizability ⟨α⟩ and first hyperpolarizability (β tot )-based properties of all compounds. A good concurrence among calculated and experimental parameters was obtained through root mean square error calculations. The molecular stability of piperidone derivatives was examined using the Hirshfeld surface and NBO analyses. Natural population analysis was also performed to obtain insights about atomic charges. Calculated HOMO−LUMO energies showed that charge transfer interactions take place within the molecules. Moreover, global reactivity parameters including electronegativity, chemical hardness, softness, ionization potential, and electrophilicity were calculated using the HOMO and LUMO energies. The average polarizability ⟨α⟩ and first hyperpolarizability (β tot ) values of all compounds were observed to be larger in magnitude at the aforesaid functional than the standard compound.

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“…Curcumin and curcumin derivatives have so far been extensively studied for therapeutic purposes, especially in parasitic infections ( Din et al, 2016 ). A successful development of a new class of curcumin has been reported against Trypanosoma cruzi ( Matiadis et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Curcumin effect on Acanthamoeba triangularis encystation under nutrient starvation

Boonhok

Sangkanu

Phumjan

et al. 2022

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Background Curcumin is an active compound derived from turmeric, Curcuma longa, and is known for its benefits to human health. The amoebicidal activity of curcumin against Acanthamoeba triangularis was recently discovered. However, a physiological change of intracellular pathways related to A. triangularis encystation mechanism, including autophagy in the surviving amoeba after curcumin treatment, has never been reported. This study aims to investigate the effect of curcumin on the survival of A. triangularis under nutrient starvation and nutrient-rich condition, as well as to evaluate the A. triangularis encystation and a physiological change of Acanthamoeba autophagy at the mRNA level. Methods In this study, A. triangularis amoebas were treated with a sublethal dose of curcumin under nutrient starvation and nutrient-rich condition and the surviving amoebas was investigated. Cysts formation and vacuolization were examined by microscopy and transcriptional expression of autophagy-related genes and other encystation-related genes were evaluated by real-time PCR. Results A. triangularis cysts were formed under nutrient starvation. However, in the presence of the autophagy inhibitor, 3-methyladenine (3-MA), the percentage of cysts was significantly reduced. Interestingly, in the presence of curcumin, most of the parasites remained in the trophozoite stage in both the starvation and nutrient-rich condition. In vacuolization analysis, the percentage of amoebas with enlarged vacuole was increased upon starvation. However, the percentage was significantly declined in the presence of curcumin and 3-MA. Molecular analysis of A. triangularis autophagy-related (ATG) genes showed that the mRNA expression of the ATG genes, ATG3, ATG8b, ATG12, ATG16, under the starvation with curcumin was at a basal level along the treatment. The results were similar to those of the curcumin-treated amoebas under a nutrient-rich condition, except AcATG16 which increased later. On the other hand, mRNA expression of encystation-related genes, cellulose synthase and serine proteinase, remained unchanged during the first 18 h, but significantly increased at 24 h post treatment. Conclusion Curcumin inhibits cyst formation in surviving trophozoites, which may result from its effect on mRNA expression of key Acanthamoeba ATG-related genes. However, further investigation into the mechanism of curcumin in A. triangularis trophozoites arrest and its association with autophagy or other encystation-related pathways is needed to support the future use of curcumin.

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Curcumin inspired synthesis of unsymmetrical diarylpentanoids with highly potent anti-parasitic activities: in silico studies and DFT-based stereochemical calculation

Abstract: Unsymmetrical diarylpentanoid analogues of curcumin have been synthesized by Claisen–Schmidt condensation of different aldehydes and ketones.

Cited by 8 publications

References 19 publications

BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

Exploration of Noncovalent Interactions, Chemical Reactivity, and Nonlinear Optical Properties of Piperidone Derivatives: A Concise Theoretical Approach

Curcumin effect on Acanthamoeba triangularis encystation under nutrient starvation

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