Research

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16 pages, 5124 KiB

Open AccessArticle

Antiparasitic Activity of Plumbago auriculata Extracts and Its Naphthoquinone Plumbagin against Trypanosoma cruzi

by Raiza Brandão Peres, Marcos Meuser Batista, Ana Luíza Rangel Bérenger, Flávia da Cunha Camillo, Maria Raquel Figueiredo and Maria de Nazaré Correia Soeiro

Pharmaceutics 2023, 15(5), 1535; https://doi.org/10.3390/pharmaceutics15051535 - 19 May 2023

Cited by 3 | Viewed by 1132

Abstract

Chagas disease (CD) caused by the protozoan Trypanosoma cruzi affects more than six million people worldwide. Treatment is restricted to benznidazole (Bz) and nifurtimox (Nf) that display low activity in the later chronic stage besides triggering toxic events that result in treatment abandonment. [...] Read more.

Chagas disease (CD) caused by the protozoan Trypanosoma cruzi affects more than six million people worldwide. Treatment is restricted to benznidazole (Bz) and nifurtimox (Nf) that display low activity in the later chronic stage besides triggering toxic events that result in treatment abandonment. Therefore, new therapeutic options are necessary. In this scenario, natural products emerge as promising alternatives to treat CD. In the family Plumbaginaceae, Plumbago sp. exhibits a broad spectrum of biological and pharmacological activities. Thus, our main objective was to evaluate, in vitro and in silico, the biological effect of crude extracts of root and of aerial parts of P. auriculata, as well as its naphthoquinone Plumbagin (Pb) against T. cruzi. The phenotypic assays revealed potent activity of the root extract against different forms (trypomastigote and intracellular forms) and strains (Y and Tulahuen), with a compound concentration that reduced 50% of the number of the parasite (EC₅₀) values ranging from 1.9 to 3.9 µg/mL. In silico analysis showed that Pb is predicted to have good oral absorption and permeability in Caco2 cells, besides excellent probability of absorption by human intestinal cells, without toxic or mutagenic potential effects, not being predicted as a substrate or inhibitor of P-glycoprotein. Pb was as potent as Bz against intracellular forms and displayed a superior trypanosomicidal effect (about 10-fold) in bloodstream forms (EC₅₀ = 0.8 µM) as compared to the reference drug (8.5 µM). The cellular targets of Pb on T. cruzi were evaluated using electron microscopy assays and the findings on bloodstream trypomastigotes showed several cellular insults related to the autophagic process. Regarding toxicity in mammalian cells, the root extracts and the naphthoquinone present a moderate toxic profile on fibroblasts and cardiac cell lines. Then, aiming to reduce host toxicity, the root extract and Pb were tested in combination with Bz, and the data showed additive profiles with the sum of the fractional inhibitory concentration indexes (ΣFICIs) being 1.45 and 0.87, respectively. Thus, our work reveals the promising antiparasitic activity of Plumbago auriculata crude extracts and its purified naphthoquinone Plumbagin against different forms and strains of Trypanosoma cruzi in vitro. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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10 pages, 1180 KiB

Open AccessArticle

Design, Synthesis and In Vitro Biological Activity of Novel C-7 Methylene Congeners of Furanoallocolchicinoids

by Iuliia A. Gracheva, Elena V. Svirshchevskaya, Ekaterina S. Shchegravina, Yulia B. Malysheva, Alsu R. Sitdikova and Alexey Yu. Fedorov

Pharmaceutics 2023, 15(4), 1034; https://doi.org/10.3390/pharmaceutics15041034 - 23 Mar 2023

Viewed by 768

Abstract

A series of novel heterocyclic colchicine derivatives bearing a C-7 methylene fragment were synthesized via Wittig, Horner–Wadsworth–Emmons and Nenajdenko–Shastin olefination approaches. The in vitro biological activities of the most promising compounds were investigated using MTT assays and cell cycle analyses. Compounds with an [...] Read more.

A series of novel heterocyclic colchicine derivatives bearing a C-7 methylene fragment were synthesized via Wittig, Horner–Wadsworth–Emmons and Nenajdenko–Shastin olefination approaches. The in vitro biological activities of the most promising compounds were investigated using MTT assays and cell cycle analyses. Compounds with an electron withdrawing group on the methylene fragment exhibited substantial antiproliferative activity towards COLO-357, BxPC-3, HaCaT, PANC-1 and A549 cell lines. The spatial orientation of the substituent at the double bond significantly influenced its biological activity. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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22 pages, 5631 KiB

Open AccessArticle

Improving Properties of Podophyllic Aldehyde-Derived Cyclolignans: Design, Synthesis and Evaluation of Novel Lignohydroquinones, Dual-Selective Hybrids against Colorectal Cancer Cells

by Ángela-Patricia Hernández, Paula Díez, Pablo A. García, Martín Pérez-Andrés, Anzhela Veselinova, Pablo G. Jambrina, Arturo San Feliciano, David Díez, Manuel Fuentes and Mᵃ Ángeles Castro

Pharmaceutics 2023, 15(3), 886; https://doi.org/10.3390/pharmaceutics15030886 - 09 Mar 2023

Cited by 2 | Viewed by 1512

Abstract

New lignohydroquinone conjugates (L-HQs) were designed and synthesized using the hybridization strategy, and evaluated as cytotoxics against several cancer cell lines. The L-HQs were obtained from the natural product podophyllotoxin and some semisynthetic terpenylnaphthohydroquinones, prepared from natural terpenoids. Both entities of the conjugates [...] Read more.

New lignohydroquinone conjugates (L-HQs) were designed and synthesized using the hybridization strategy, and evaluated as cytotoxics against several cancer cell lines. The L-HQs were obtained from the natural product podophyllotoxin and some semisynthetic terpenylnaphthohydroquinones, prepared from natural terpenoids. Both entities of the conjugates were connected through different aliphatic or aromatic linkers. Among the evaluated hybrids, the L-HQ with the aromatic spacer clearly displayed the in vitro dual cytotoxic effect derived from each starting component, retaining the selectivity and showing a high cytotoxicity at short (24 h) and long (72 h) incubation times (4.12 and 0.0450 µM, respectively) against colorectal cancer cells. In addition, the cell cycle blockade observed by flow cytometry studies, molecular dynamics, and tubulin interaction studies demonstrated the interest of this kind of hybrids, which docked adequately into the colchicine binding site of tubulin despite their large size. These results prove the validity of the hybridization strategy and encourage further research on non-lactonic cyclolignans. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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17 pages, 8810 KiB

Open AccessArticle

Effects of Mangiferin on LPS-Induced Inflammation and SARS-CoV-2 Viral Adsorption in Human Lung Cells

by Mariarita Spampinato, Giuseppe Carota, Giuseppe Sferrazzo, Virginia Fuochi, Alfio Distefano, Simone Ronsisvalle, Federica Sipala, Rosario Giuffrida, Pio Maria Furneri, Michelino Di Rosa, Daniele Tibullo, Giovanni Li Volti and Ignazio Barbagallo

Pharmaceutics 2022, 14(12), 2845; https://doi.org/10.3390/pharmaceutics14122845 - 19 Dec 2022

Cited by 3 | Viewed by 1751

Abstract

The growing interest in natural bioactive molecules, as an approach to many pathological contexts, is widely justified by the necessity to overcome the disadvantageous benefit–risk ratio related to traditional therapies. Among them, mangiferin (MGF) shows promising beneficial properties such as antioxidant, anti-inflammatory, and [...] Read more.

The growing interest in natural bioactive molecules, as an approach to many pathological contexts, is widely justified by the necessity to overcome the disadvantageous benefit–risk ratio related to traditional therapies. Among them, mangiferin (MGF) shows promising beneficial properties such as antioxidant, anti-inflammatory, and immunomodulatory effects. In this study, we aimed to investigate the antioxidant and anti-inflammatory properties of MGF on lipopolysaccharide (LPS)-induced lung NCI-H292 cells, focusing on its role against COVID-19 adsorption. In order to obtain this information, cells treated with LPS, with or without MGF, were analyzed performing wound healing, gene expression of inflammatory cytokines, GSH quantification, and JC-1 staining. Moreover, the inhibition of viral adsorption was evaluated microbiologically and the results were further confirmed by molecular docking analysis. In this regard, MGF downregulates the expression of several inflammatory factors, enhances GSH levels, promotes the wound healing rate, and restores the mitochondrial dysfunction caused by LPS. In addition, MGF significantly inhibits SARS-CoV-2 adsorption as shown by the gene expression of ACE2 and TMPRSS-2, and furtherly confirmed by microbiological and molecular modeling evaluation. Although more investigations are still needed, all data obtained constitute a solid background, demonstrating the cytoprotective role of MGF in inflammatory mechanisms including COVID-19 infection. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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14 pages, 1922 KiB

Open AccessArticle

Analgesic and Anti-Inflammatory Properties of Ethanolic Extract of Piper vicosanum Leaves

by Armando Jorge Junior, Joyce dos Santos Lencina, Elisangela dos Santos, Jonas da Silva Mota, Roberto Kenji Nakamura Cuman, Elisabete Castelon Konkiewitz, Cândida Aparecida Leite Kassuya and Saulo Euclides Silva-Filho

Pharmaceutics 2022, 14(11), 2455; https://doi.org/10.3390/pharmaceutics14112455 - 14 Nov 2022

Viewed by 1242

Abstract

Nonclinical trials are important to validate the efficacy and safety of medicinal plants. Scientific toxicological studies with Piper vicosanum Yuncker have showed its safety; however, no studies have indicated the analgesic or antiarthritic potential of the ethanolic extract of P. vicosanum leaves (EEPV). [...] Read more.

Nonclinical trials are important to validate the efficacy and safety of medicinal plants. Scientific toxicological studies with Piper vicosanum Yuncker have showed its safety; however, no studies have indicated the analgesic or antiarthritic potential of the ethanolic extract of P. vicosanum leaves (EEPV). The objective of the present work was to evaluate the antiarthritic and antinociceptive effects of EEPV in experimental mouse models. The oral administration of EEPV (100, 300, and 700 mg/kg) and dexamethasone (1 mg/kg) were performed in carrageenan-induced pleurisy, in formalin and acetic-acid-induced nociception, and in zymosan-induced articular inflammation models in Swiss mice. The EEPV (300 mg/kg) was tested in zymosan-articular inflammation, the complete Freund’s adjuvant (CFA) inflammatory model, and in in situ intravitreal microscopy analysis of rolling and adhesion events of leukocytes in the mesenteric microcirculation in mice. EEPV significantly inhibited: (i) nociceptive response at phase 1 and 2, and also in the cold response in the formalin model; (ii) abdominal contortion induced by acetic acid; (iii) mechanical hyperalgesia after 4 and 6 h, knee edema after 6 h, and leukocyte migration in articular inflammation induced by zymosan. All doses of EEPV reduced the leukocyte migration to the inflamed pleural cavity and knee edema 4 h after the zymosan knee injection. The treatment with the EEPV significantly inhibited the CFA-induced edema, mechanical and cold hyperalgesia, and NAG and MPO. The EEPV also significantly inhibited carrageenan-induced leukocyte rolling and adhesion. The present study revealed, for the first time, the antiarthritic and antinociceptive effects of the EEPV. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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17 pages, 4291 KiB

Open AccessArticle

Comparative Evaluation of the Antiglycation and Anti-α-Glucosidase Activities of Baicalein, Baicalin (Baicalein 7-O-Glucuronide) and the Antidiabetic Drug Metformin

by Guglielmina Froldi, Francine Medjiofack Djeujo, Nadia Bulf, Emma Caparelli and Eugenio Ragazzi

Pharmaceutics 2022, 14(10), 2141; https://doi.org/10.3390/pharmaceutics14102141 - 09 Oct 2022

Cited by 5 | Viewed by 1626

Abstract

The discovery of new oral antidiabetic drugs remains a priority in medicine. This research aimed to evaluate the activity of the flavonoid baicalein and its natural glucuronide baicalin, compared to the antidiabetic drug metformin, as potential antiglycation, anti–radical, and anti-α–glucosidase agents, in order [...] Read more.

The discovery of new oral antidiabetic drugs remains a priority in medicine. This research aimed to evaluate the activity of the flavonoid baicalein and its natural glucuronide baicalin, compared to the antidiabetic drug metformin, as potential antiglycation, anti–radical, and anti-α–glucosidase agents, in order to assess their potential role in counteracting hyperglycemia-induced tissue damage. The study considered: (i) the BSA assay, to detect the formation of advanced glycation end products (AGEs), (ii) the GK peptide–ribose assay, which evaluates the cross–linking between the peptide and ribose, and (iii) the carbonyl content assay to detect the total carbonyl content, as a biomarker of tissue damage. In addition, to obtain a reliable picture of the antiglycation capacity of the investigated compounds, DPPH scavenging and oxygen radical absorbance capacity (ORAC) assays were performed. Furthermore, the anti–α–glucosidase activity of baicalein and baicalin was detected. Furthermore, to estimate cell permeability, preliminarily, the cytotoxicity of baicalein and baicalin was evaluated in HT–29 human colon adenocarcinoma cells using the MTT assay. Successively, the ability of the compounds to pass through the cytoplasmic membranes of HT–29 cells was detected as a permeability screen to predict in vivo absorption, showing that baicalein passes into cells even if it is quickly modified in various metabolites, being its main derivative baicalin. Otherwise, baicalin per se did not pass through cell membranes. Data show that baicalein is the most active compound in reducing glycation, α-glucosidase activity, and free radicals, while baicalin exhibited similar activities, but did not inhibit the enzyme α–glucosidase. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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17 pages, 5206 KiB

Open AccessArticle

In Vitro and In Silico Potential Inhibitory Effects of New Biflavonoids from Ochna rhizomatosa on HIV-1 Integrase and Plasmodium falciparum

by Angélique Nicolas Messi, Susan Lucia Bonnet, Brice Ayissi Owona, Anke Wilhelm, Eutrophe Le Doux Kamto, Joseph Thierry Ndongo, Xavier Siwe-Noundou, Madan Poka, Patrick H. Demana, Rui W. M. Krause, Joséphine Ngo Mbing, Dieudonné Emmanuel Pegnyemb and Christian G. Bochet

Pharmaceutics 2022, 14(8), 1701; https://doi.org/10.3390/pharmaceutics14081701 - 15 Aug 2022

Cited by 2 | Viewed by 2349

Abstract

The aim of this study was to identify bioactive secondary metabolites from Ochna rhizomatosa with potential inhibitory effects against HIV and Plasmodium falciparum. A phytochemical study of O. rhizomatosa root barks resulted in the identification of three new biflavonoids (1–3 [...] Read more.

The aim of this study was to identify bioactive secondary metabolites from Ochna rhizomatosa with potential inhibitory effects against HIV and Plasmodium falciparum. A phytochemical study of O. rhizomatosa root barks resulted in the identification of three new biflavonoids (1–3), along with four known ones (4–7). Compound 7 (Gerontoisoflavone A) was a single flavonoid present in the rootbark of the plant and was used as a reference. Compound 1 (IC₅₀ = 0.047 µM) was the only one with a noteworthy inhibitory effect against HIV-1 integrase in vitro. Chicoric acid (IC₅₀ = 0.006 µM), a pure competitive inhibitor of HIV-1 integrase, was used as control. Compound 2 exhibited the highest antiplasmodial activity (IC₅₀ = 4.60 µM) against the chloroquine-sensitive strain of Plasmodium falciparum NF54. Computational molecular docking revealed that compounds 1 and 2 had the highest binding score (−121.8 and −131.88 Kcal/mol, respectively) in comparison to chicoric acid and Dolutegravir (−116 and −100 Kcal/mol, respectively), towards integrase receptor (PDB:3LPT). As far as Plasmodium-6 cysteine s48/45 domain inhibition is concerned, compounds 1 and 2 showed the highest binding scores in comparison to chloroquine, urging the analysis of these compounds in vivo for disease treatment. These results confirm the potential inhibitory effect of compounds 1 and 2 for HIV and malaria treatment. Therefore, our future investigation to find inhibitors of these receptors in vivo could be an effective strategy for developing new drugs. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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Review

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41 pages, 16719 KiB

Open AccessReview

Synthesis and Modification of Morphine and Codeine, Leading to Diverse Libraries with Improved Pain Relief Properties

by Mona Kamelan Zargar Zarin, Wim Dehaen, Peyman Salehi and Amir Ata Bahmani Asl

Pharmaceutics 2023, 15(6), 1779; https://doi.org/10.3390/pharmaceutics15061779 - 20 Jun 2023

Cited by 2 | Viewed by 3363

Abstract

Morphine and codeine, two of the most common opioids, are widely used in the clinic for different types of pain. Morphine is one of the most potent agonists for the μ-opioid receptor, leading to the strongest analgesic effect. However, due to their [...] Read more.

Morphine and codeine, two of the most common opioids, are widely used in the clinic for different types of pain. Morphine is one of the most potent agonists for the μ-opioid receptor, leading to the strongest analgesic effect. However, due to their association with serious side effects such as respiratory depression, constriction, euphoria, and addiction, it is necessary for derivatives of morphine and codeine to be developed to overcome such drawbacks. The development of analgesics based on the opiate structure that can be safe, orally active, and non-addictive is one of the important fields in medicinal chemistry. Over the years, morphine and codeine have undergone many structural changes. The biological investigation of semi-synthetic derivatives of both morphine and codeine, especially morphine, shows that studies on these structures are still significant for the development of potent opioid antagonists and agonists. In this review, we summarize several decade-long attempts to synthesize new analogues of morphine and codeine. Our summary placed a focus on synthetic derivatives derived from ring A (positions 1, 2, and 3), ring C (position 6), and N-17 moiety. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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31 pages, 4635 KiB

Open AccessReview

Immunomodulatory Properties of Natural Extracts and Compounds Derived from Bidens pilosa L.: Literature Review

by Xandy Melissa Rodríguez-Mesa, Leonardo Andres Contreras Bolaños, Antonio Mejía, Luis Miguel Pombo, Geison Modesti Costa and Sandra Paola Santander González

Pharmaceutics 2023, 15(5), 1491; https://doi.org/10.3390/pharmaceutics15051491 - 13 May 2023

Cited by 3 | Viewed by 2346

Abstract

Bidens pilosa L. has been used in different parts of the world mainly to treat diseases associated with immune response disorders, such as autoimmunity, cancer, allergies, and infectious diseases. The medicinal properties of this plant are attributed to its chemical components. Nevertheless, there [...] Read more.

Bidens pilosa L. has been used in different parts of the world mainly to treat diseases associated with immune response disorders, such as autoimmunity, cancer, allergies, and infectious diseases. The medicinal properties of this plant are attributed to its chemical components. Nevertheless, there is little conclusive evidence that describes the immunomodulatory activity of this plant. In this review, a systematic search was carried out in the PubMed-NLM, EBSCO Host and BVS databases focused on the pre-clinical scientific evidence of the immunomodulatory properties of B. pilosa. A total of 314 articles were found and only 23 were selected. The results show that the compounds or extracts of Bidens modulate the immune cells. This activity was associated with the presence of phenolic compounds and flavonoids that control proliferation, oxidative stress, phagocytosis, and the production of cytokines of different cells. Most of the scientific information analyzed in this paper supports the potential use of B. pilosa mainly as an anti-inflammatory, antioxidant, antitumoral, antidiabetic, and antimicrobial immune response modulator. It is necessary that this biological activity be corroborated through the design of specialized clinical trials that demonstrate the effectiveness in the treatment of autoimmune diseases, chronic inflammation, and infectious diseases. Until now there has only been one clinical trial in phase I and II associated with the anti-inflammatory activity of Bidens in mucositis. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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20 pages, 1449 KiB

Open AccessReview

Apoptotic Mechanisms of Quercetin in Liver Cancer: Recent Trends and Advancements

by Gautam Sethi, Prangya Rath, Abhishek Chauhan, Anuj Ranjan, Renuka Choudhary, Seema Ramniwas, Katrin Sak, Diwakar Aggarwal, Isha Rani and Hardeep Singh Tuli

Pharmaceutics 2023, 15(2), 712; https://doi.org/10.3390/pharmaceutics15020712 - 20 Feb 2023

Cited by 22 | Viewed by 3876

Abstract

Due to rising incidence rates of liver cancer and worries about the toxicity of current chemotherapeutic medicines, the hunt for further alternative methods to treat this malignancy has escalated. Compared to chemotherapy, quercetin, a flavonoid, is relatively less harmful to normal cells and [...] Read more.

Due to rising incidence rates of liver cancer and worries about the toxicity of current chemotherapeutic medicines, the hunt for further alternative methods to treat this malignancy has escalated. Compared to chemotherapy, quercetin, a flavonoid, is relatively less harmful to normal cells and is regarded as an excellent free-radical scavenger. Apoptotic cell death of cancer cells caused by quercetin has been demonstrated by many prior studies. It is present in many fruits, vegetables, and herbs. Quercetin targets apoptosis, by upregulating Bax, caspase-3, and p21 while downregulating Akt, PLK-1, cyclin-B1, cyclin-A, CDC-2, CDK-2, and Bcl-2. Additionally, it has been reported to increase STAT3 protein degradation in liver cancer cells while decreasing STAT3 activation. Quercetin has a potential future in chemoprevention, based on substantial research on its anticancer effects. The current review discusses quercetin’s mechanisms of action, nanodelivery strategies, and other potential cellular effects in liver cancer. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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21 pages, 1217 KiB

Open AccessReview

Oral Pharmacokinetics of Hydroxycinnamic Acids: An Updated Review

by Kleyton Santos Veras, Flávia Nathiely Silveira Fachel, Bibiana Verlindo de Araújo, Helder Ferreira Teixeira and Letícia Scherer Koester

Pharmaceutics 2022, 14(12), 2663; https://doi.org/10.3390/pharmaceutics14122663 - 30 Nov 2022

Cited by 7 | Viewed by 1708

Abstract

Hydroxycinnamic acids (HCAs) such as caffeic acid (CA), chlorogenic acid (CGA), coumaric acid (COA) isomers, ferulic acid (FA) and rosmarinic acid (RA) are natural phenolic acids with widespread distribution in vegetal foods and well-documented pharmacological activities. However, the low bioavailability of HCAs impairs [...] Read more.

Hydroxycinnamic acids (HCAs) such as caffeic acid (CA), chlorogenic acid (CGA), coumaric acid (COA) isomers, ferulic acid (FA) and rosmarinic acid (RA) are natural phenolic acids with widespread distribution in vegetal foods and well-documented pharmacological activities. However, the low bioavailability of HCAs impairs their administration by the oral route. The present review addresses new findings and important factors/obstacles for their oral administration, which were unexplored in the reviews published a decade ago concerning the bioavailability of phenolic acids. Based on this, the article aims to perform an updated review of the water solubility and gastrointestinal stability of HCAs, as well as describe their oral absorption, distribution, metabolism and excretion (ADME) processes by in vitro, ex vivo, in situ and in vivo methods. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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26 pages, 4332 KiB

Open AccessReview

Gossypol and Its Natural Derivatives: Multitargeted Phytochemicals as Potential Drug Candidates for Oncologic Diseases

by Dilipkumar Pal, Pooja Sahu, Gautam Sethi, Carly E. Wallace and Anupam Bishayee

Pharmaceutics 2022, 14(12), 2624; https://doi.org/10.3390/pharmaceutics14122624 - 28 Nov 2022

Cited by 8 | Viewed by 3531

Abstract

Despite the vast amounts of research and remarkable discoveries that have been made in recent decades, cancer remains a leading cause of death and a major public health concern worldwide. Gossypol, a natural polyphenolic compound derived from the seeds, roots, and stems of [...] Read more.

Despite the vast amounts of research and remarkable discoveries that have been made in recent decades, cancer remains a leading cause of death and a major public health concern worldwide. Gossypol, a natural polyphenolic compound derived from the seeds, roots, and stems of cotton (Gossypium hirsutum L.), was first used as a male contraceptive agent. Due to its diverse biological properties, including antifertility, antiviral, antioxidant, antibacterial, antimalarial, and most notably antitumor activities, gossypol has been the subject of numerous studies. Nevertheless, no systematic review has been performed that analyzes the antineoplastic potential of gossypol and related natural compounds in an organ-specific manner while delineating the molecular mechanisms of action. Hence, we have performed an extensive literature search for anticancer properties of gossypol and their natural derivatives against various types of cancer cells utilizing PubMed, ScienceDirect, Google Scholar, and Scopus. The sources, distribution, chemical structure, and toxicity of gossypol and its constituents are briefly reviewed. Based on emerging evidence, gossypol and related compounds exhibit significant antineoplastic effects against various cancer types through the modulation of different cancer hallmarks and signaling pathways. Additionally, the synergistic activity of gossypol and its derivatives with chemotherapeutic agents has been observed. Our evaluation of the current literature suggests the potential of gossypol and its derivatives as multitargeting drug candidates to combat multiple human malignancies. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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28 pages, 3970 KiB

Open AccessEditor’s ChoiceReview

Beyond Formulation: Contributions of Nanotechnology for Translation of Anticancer Natural Products into New Drugs

by Rodrigo dos A. Miguel, Amanda S. Hirata, Paula C. Jimenez, Luciana B. Lopes and Leticia V. Costa-Lotufo

Pharmaceutics 2022, 14(8), 1722; https://doi.org/10.3390/pharmaceutics14081722 - 17 Aug 2022

Cited by 16 | Viewed by 3004

Abstract

Nature is the largest pharmacy in the world. Doxorubicin (DOX) and paclitaxel (PTX) are two examples of natural-product-derived drugs employed as first-line treatment of various cancer types due to their broad mechanisms of action. These drugs are marketed as conventional and nanotechnology-based formulations, [...] Read more.

Nature is the largest pharmacy in the world. Doxorubicin (DOX) and paclitaxel (PTX) are two examples of natural-product-derived drugs employed as first-line treatment of various cancer types due to their broad mechanisms of action. These drugs are marketed as conventional and nanotechnology-based formulations, which is quite curious since the research and development (R&D) course of nanoformulations are even more expensive and prone to failure than the conventional ones. Nonetheless, nanosystems are cost-effective and represent both novel and safer dosage forms with fewer side effects due to modification of pharmacokinetic properties and tissue targeting. In addition, nanotechnology-based drugs can contribute to dose modulation, reversion of multidrug resistance, and protection from degradation and early clearance; can influence the mechanism of action; and can enable drug administration by alternative routes and co-encapsulation of multiple active agents for combined chemotherapy. In this review, we discuss the contribution of nanotechnology as an enabling technology taking the clinical use of DOX and PTX as examples. We also present other nanoformulations approved for clinical practice containing different anticancer natural-product-derived drugs. Full article

(This article belongs to the Special Issue Recent Advances in Natural Product Drugs)

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