Combretastatin A4-camptothecin micelles as combination therapy for effective anticancer activity

Assali, Mohyeddin; Kittana, Naim; Qasem, Sahar Alhaj; Adas, Raghad; Saleh, Doaa; Arar, Asala; Zohud, Osayd

doi:10.1039/c8ra08794f

Cited by 17 publications

(12 citation statements)

References 48 publications

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“…Combining combretastatin and camptothecin molecules by an ester moiety can be an example of such a structure. This molecule can form micelles, which may improve solubility with higher cytotoxicity compared to the original drugs [106]. The combination with platinum derivatives also perfectly fits into the above strategy ( Figure 5) [134].…”

Section: Modifications Of the Hydroxyl Group Of Combretastatin Coresupporting

confidence: 53%

“…Although combretastatin-based compounds exert prominent anticancer activity, some disadvantages, such as (i) the isomerization of its stilbene Z-double bond into the less active E-form during storage, administration, and metabolism; (ii) low water solubility, and (iii) the non-selective targeting, may limit the transfer to clinics [103,104]. Starting from combretastatin A-4 phosphate (CA-4P, fosbretabulin), more water-soluble update version of CA-4, medicinal chemistry offers further advanced derivatives and formulation such as theranostic nanocarriers [105,106], nanodrugs [107], hypoxia-activated prodrugs [108,109], and others. The remarkable potential of combretastatin analogues is borne out by the fact that currently, CA-4P is studied under several clinical trials as a monotherapy, and combining therapy with other chemotherapeutic agents, such as pazopanib, paclitaxel, carboplatin, or bevacizumab [103].…”

Section: Combretastatins-between Bench and Bedsidementioning

confidence: 99%

“…In general, this approach is based on (i) merging the structural features of different drugs, (ii) conjugating two drugs or pharmacophores via cleavable/non-cleavable linkers [113]. To date, several hybrids linking combretastatin with other active molecules such as celecoxib pharmacophore [114], β-carboline [115], camptothecin [106], and cisplatin have synthesized as promising anticancer agents. Following this strategy, Punganuru et al designed the piperlongumine (PL) derivatives with an aryl group inserted at the C-7 position [116].…”

Section: Modification Of the Aromatic Ringmentioning

confidence: 99%

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More Than Resveratrol: New Insights into Stilbene-Based Compounds

et al. 2020

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The concept of a scaffold concerns many aspects at different steps on the drug development path. In medicinal chemistry, the choice of relevant “drug-likeness” scaffold is a starting point for the design of the structure dedicated to specific molecular targets. For many years, the chemical uniqueness of the stilbene structure has inspired scientists from different fields such as chemistry, biology, pharmacy, and medicine. In this review, we present the outstanding potential of the stilbene-based derivatives. Naturally occurring stilbenes, together with powerful synthetic chemistry possibilities, may offer an excellent approach for discovering new structures and identifying their therapeutic targets. With the development of scientific tools, sophisticated equipment, and a better understanding of the disease pathogenesis at the molecular level, the stilbene scaffold has moved innovation in science. This paper mainly focuses on the stilbene-based compounds beyond resveratrol, which are particularly attractive due to their biological activity. Given the “fresh outlook” about different stilbene-based compounds starting from stilbenoids with particular regard to isorhapontigenin and methoxy- and hydroxyl- analogues, the update about the combretastatins, and the very often overlooked and underestimated benzanilide analogues, we present a new story about this remarkable structure.

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Section: Modifications Of the Hydroxyl Group Of Combretastatin Coresupporting

confidence: 53%

Section: Combretastatins-between Bench and Bedsidementioning

confidence: 99%

Section: Modification Of the Aromatic Ringmentioning

confidence: 99%

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More Than Resveratrol: New Insights into Stilbene-Based Compounds

et al. 2020

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“…e synthesized codrug was incubated with an esterase enzyme to study its hydrolysis to its parent drugs (IND & PAR). is was achieved by incubating 1 mg of codrug into 10 mL phosphate buffer saline solution (pH 7.4) containing 1 mg of esterase enzyme (10 U) at 37°C for 1 h [31][32][33]. At different time intervals, aliquots of 1 mL were obtained, and then the concentrations were analyzed by the developed HPLC method.…”

Section: Hydrolysis Of Codrugmentioning

confidence: 99%

RP-HPLC Method Development and Validation of Synthesized Codrug in Combination with Indomethacin, Paracetamol, and Famotidine

Assali

Abualhasan

Zohud

et al. 2020

International Journal of Analytical Chemistry

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Background. Indomethacin is considered a potent nonsteroidal anti-inflammatory drug that could be combined with Paracetamol to have superior and synergist activity to manage pain and inflammation. To reduce the gastric side effect, they could be combined with Famotidine. Methodology. A codrug of Indomethacin and Paracetamol was synthesized and combined in solution with Famotidine. The quantification of the pharmaceutically active ingredients is pivotal in the development of pharmaceutical formulations. Therefore, a novel reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated according to the International Council for Harmonization (ICH) Q2R1 guidelines. A reverse phase C18 column with a mobile phase acetonitrile: sodium acetate buffer 60 : 40 at a flow rate of 1.4 mL/min and pH 5 was utilized. Results. The developed method showed good separation of the four tested drugs with a linear range of 0.01–0.1 mg/mL (R2 > 0.99). The LODs for FAM, PAR, IND, and codrug were 3.076 × 10−9, 3.868 × 10−10, 1.066 × 10−9, and 4.402 × 10−9 mg/mL respectively. While the LOQs were 9.322 × 10−9, 1.172 × 10−10, 3.232 × 10−9, and 1.334 × 10−8 mg/mL, respectively. Furthermore, the method was precise, accurate, selective, and robust with values of relative standard deviation (RSD) less than 2%. Moreover, the developed method was applied to study the in vitro hydrolysis and conversion of codrug into Indomethacin and Paracetamol. Conclusion. The codrug of Indomethacin and Paracetamol was successfully synthesized for the first time. Moreover, the developed analytical method, to our knowledge, is the first of its kind to simultaneously quantify four solutions containing the following active ingredients of codrug, Indomethacin, Paracetamol, and Famotidine mixture with added pharmaceutical inactive ingredients in one HPLC run.

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“…The nanoplatform with a release time of 3−7 days was shown to have the best tumor suppression effect. In another study, CA4 and camptothecin were loaded into a self‐assembled micelle, which was able to improve its water solubility and anti‐tumor activity (Assali et al, 2019). In order to control drug release, in situ thermo‐gelling hydrogel equipped with CA4 and cisplatin (CDDP) was prepared for the treatment of a colon cancer model (S. Yu et al, 2019).…”

Section: Engineered Nanomedicines For Vascular Disruption Strategymentioning

confidence: 99%

Engineered nanomedicines for tumor vasculature blockade therapy

Zhao

Huang

Zhang

et al. 2021

WIREs Nanomed Nanobiotechnol

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Tumor vasculature blockade therapy (TVBT), including angiogenesis inhibition, vascular disruption, and vascular infarction, provides a promising treatment modality for solid tumors. However, low selectivity, drug resistance, and possible severe side effects have limited the clinical transformation of TVBT. Engineered nanoparticles offer potential solutions, including prolonged circulation time, targeted transportation, and controlled release of TVBT agents. Moreover, engineered nanomedicines provide a promising combination platform of TVBT with chemotherapy, radiotherapy, photodynamic therapy, photothermal therapy, ultrasound therapy, and gene therapy. In this article, we offer a comprehensive summary of the current progress of engineered nanomedicines for TVBT and also discuss current deficiencies and future directions for TVBT development. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies

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Combretastatin A4-camptothecin micelles as combination therapy for effective anticancer activity

Abstract: Novel CA4-TEG-triazole-TEG-Cpt (codrug 9) was synthesized and self-assembled into a micelle structure that showed a great synergistic anticancer activity on HeLa cancer cells without affecting the viability of 3T3 normal cells.

Cited by 17 publications

References 48 publications

More Than Resveratrol: New Insights into Stilbene-Based Compounds

More Than Resveratrol: New Insights into Stilbene-Based Compounds

RP-HPLC Method Development and Validation of Synthesized Codrug in Combination with Indomethacin, Paracetamol, and Famotidine

Engineered nanomedicines for tumor vasculature blockade therapy

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