scholarly journals Anticancer Potential of Betulonic Acid Derivatives

2021 ◽  
Vol 22 (7) ◽  
pp. 3676
Author(s):  
Adelina Lombrea ◽  
Alexandra Denisa Scurtu ◽  
Stefana Avram ◽  
Ioana Zinuca Pavel ◽  
Māris Turks ◽  
...  

Clinical trials have evidenced that several natural compounds, belonging to the phytochemical classes of alkaloids, terpenes, phenols and flavonoids, are effective for the management of various types of cancer. Latest research has proven that natural products and their semisynthetic variants may serve as a starting point for new drug candidates with a diversity of biological and pharmacological activities, designed to improve bioavailability, overcome cellular resistance, and enhance therapeutic efficacy. This review was designed to bring an update regarding the anticancer potential of betulonic acid and its semisynthetic derivatives. Chemical derivative structures of betulonic acid including amide, thiol, and piperidine groups, exert an amplification of the in vitro anticancer potential of betulonic acid. With the need for more mechanistic and in vivo data, some derivatives of betulonic acids may represent promising anticancer agents.

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6012 ◽  
Author(s):  
Rumana Ahmad

BackgroundSolanum nigrum(black nightshade;S. nigrum), a member of family Solanaceae, has been endowed with a heterogeneous array of secondary metabolites of which the steroidal glycoalkaloids (SGAs) and steroidal saponins (SS) have vast potential to serve as anticancer agents. Since there has been much controversy regarding safety of use of glycoalkaloids as anticancer agents, this area has remained more or less unexplored. Cytoskeletal proteins like actin play an important role in maintaining cell shape, synchronizing cell division, cell motility, etc. and along with their accessory proteins may also serve as important therapeutic targets for potential anticancer candidates. In the present study, glycoalkaloids and saponins fromS. nigrumwere screened for their interaction and binding affinity to cytoskeletal proteins, using molecular docking.MethodsBioactivity score and Prediction of Activity Spectra for Substances (PASS) analysis were performed using softwares Molinspiration and Osiris Data Explorer respectively, to assess the feasibility of selected phytoconstituents as potential drug candidates. The results were compared with two standard reference drugs doxorubicin hydrochloride (anticancer) and tetracycline (antibiotic). Multivariate data obtained were analyzed using principal component analysis (PCA).ResultsDocking analysis revealed that the binding affinities of the phytoconstituents towards the target cytoskeletal proteins decreased in the order coronin>villin>ezrin>vimentin>gelsolin>thymosin>cofilin. Glycoalkaloid solasonine displayed the greatest binding affinity towards the target proteins followed by alpha-solanine whereas amongst the saponins, nigrumnin-I showed maximum binding affinity. PASS Analysis of the selected phytoconstituents revealed 1 to 3 violations of Lipinski’s parameters indicating the need for modification of their structure-activity relationship (SAR) for improvement of their bioactivity and bioavailability. Glycoalkaloids and saponins all had bioactivity scores between −5.0 and 0.0 with respect to various receptor proteins and target enzymes. Solanidine, solasodine and solamargine had positive values of druglikeness which indicated that these compounds have the potential for development into future anticancer drugs. Toxicity potential evaluation revealed that glycoalkaloids and saponins had no toxicity, tumorigenicity or irritant effect(s). SAR analysis revealed that the number, type and location of sugar or the substitution of hydroxyl group on alkaloid backbone had an effect on the activity and that the presence of α-L-rhamnopyranose sugar at C-2 was critical for a compound to exhibit anticancer activity.ConclusionThe present study revealed some cytoskeletal target(s) forS. nigrumphytoconstituents by docking analysis that have not been previously reported and thus warrant further investigations bothin vitroandin vivo.


2021 ◽  
Vol 22 (22) ◽  
pp. 12255
Author(s):  
Niti Sharma ◽  
Mario A. Tan ◽  
Seong Soo A. An

Phytosterols constitute a class of natural products that are an important component of diet and have vast applications in foods, cosmetics, and herbal medicines. With many and diverse isolated structures in nature, they exhibit a broad range of biological and pharmacological activities. Among over 200 types of phytosterols, stigmasterol and β-sitosterol were ubiquitous in many plant species, exhibiting important aspects of activities related to neurodegenerative diseases. Hence, this mini-review presented an overview of the reported studies on selected phytosterols related to neurodegenerative diseases. It covered the major phytosterols based on biosynthetic considerations, including other phytosterols with significant in vitro and in vivo biological activities.


Author(s):  
Nyamsuren E ◽  
Odontuya G

In this review, we summarized the molecular structure specification of a unique component named as phenylethanoid glycosides from the genus Pedicularis L. and their biological and pharmacological activities. Until now, 40 phenylethanoid glycosides have been isolated and identified from the genus Pedicularis L. We classified the compounds into 4 main groups based on the functional group located at the 4′ position. According to the results of in vitro and in vivo studies, the extract containing phenylethanoid glycosides possesses antioxidative, antibacterial, anti-tumor and anti-fatigue activities as well as the increase in physical ability, hepatoprotection, and other effects. The antioxidant effect is the main biological activity of phenylethanoid glycosides. Хувилангын зүйл ургамлуудын фенилэтаноид гликозидуудын химийн бүтэц, биолог, фармакологийн идэвх Хураангуй: Бид энэхүү тойм өгүүлэлдээ Хувилангын (Pedicularis L.) төрөлд хамаарах ургамлуудын өвөрмөц бүрэлдэхүүн болох фенилэтаноид гликозидийн молекулын бүтцийн онцлог, тэдгээрийн биолог, фармакологийн идэвхийн судалгааны дүнг нэгтгэн бичлээ. Өнөөг хүртэл Хувилангын зүйл ургамлуудаас 40 фенилэтаноид гликозидийг ялгаж, бүтэц байгууламжийг тогтоосон байна. Бид тэдгээр бодисын молекулын бүтцэд дүн шинжилгээ хийж 4′ байрлал дахь халагч бүлэгт үндэслэн 4 бүлэгт ангилав. Фенилэтаноид гликозид зонхилонагуулагддаг ханд нь исэлдэлтийн эсрэг, бактер, хорт хавдрын эсийн өсөлтийг дарангуйлах идэвхтэй, ядралт багасгах, булчингийн үйл ажиллагааг дэмжих, элэг, тархийг гэмтэхээс хамгаалах үйлдэл үзүүлж байгаа нь in vitro ба in vivo туршилт судалгааны дүн харуулж байна. Исэлдэлтийг дарангуйлах үйлдэл бол фенилэтаноид гликозидуудын гол биологийн идэвх юм.Түлхүүр үг: Хувиланга, фенилэтаноид гликозид, каффейны хүчил, исэлдэлт дарангуйлах идэвх.


2019 ◽  
Vol 70 (3) ◽  
pp. 943-945
Author(s):  
Zsolt Gyori ◽  
Monica Susan ◽  
Razvan Susan ◽  
Andrada Iftode ◽  
Cristina Trandafirescu ◽  
...  

As prophylactic and therapeutic approaches for melanoma, of great interest and importance are the in vitro studies using cell lines to elucidate several tumoral phenomena. Therefore, the similarities and differences between the different tumor cells must be known and understood in order to obtain a more accurate correlation with processes that occur in vivo. In this study, six cell lines of melanoma, both of mouse and human origin were analyzed from the point of view of cell culture growth, morphology and use in the research of new therapies. In brief, the current paper exhibits a comparison of melanoma cells which can be utilized as a starting point for further in vitro studies and in vivo animal models.


2019 ◽  
Vol 26 (25) ◽  
pp. 4799-4831 ◽  
Author(s):  
Jiahua Cui ◽  
Xiaoyang Liu ◽  
Larry M.C. Chow

P-glycoprotein, also known as ABCB1 in the ABC transporter family, confers the simultaneous resistance of metastatic cancer cells towards various anticancer drugs with different targets and diverse chemical structures. The exploration of safe and specific inhibitors of this pump has always been the pursuit of scientists for the past four decades. Naturally occurring flavonoids as benzopyrone derivatives were recognized as a class of nontoxic inhibitors of P-gp. The recent advent of synthetic flavonoid dimer FD18, as a potent P-gp modulator in reversing multidrug resistance both in vitro and in vivo, specifically targeted the pseudodimeric structure of the drug transporter and represented a new generation of inhibitors with high transporter binding affinity and low toxicity. This review concerned the recent updates on the structure-activity relationships of flavonoids as P-gp inhibitors, the molecular mechanisms of their action and their ability to overcome P-gp-mediated MDR in preclinical studies. It had crucial implications on the discovery of new drug candidates that modulated the efflux of ABC transporters and also provided some clues for the future development in this promising area.


2020 ◽  
Vol 26 ◽  
Author(s):  
Shaik Ibrahim Khalivulla ◽  
Arifullah Mohammed ◽  
Kokkanti Mallikarjuna

Background: Diabetes is a chronic disease affecting a large population worldwide and stands as one of the major global health challenges to be tackled. According to World Health Organization, about 400 million are having diabetes worldwide and it is the seventh leading cause of deaths in 2016. Plant based natural products had been in use from ancient time as ethnomedicine for the treatment of several diseases including diabetes. As a result of that, there are several reports on plant based natural products displaying antidiabetic activity. In the current review, such antidiabetic potential compounds reported from all plant sources along with their chemical structures are collected, presented and discussed. This kind of reports are essential to pool the available information to one source followed by statistical analysis and screening to check the efficacy of all known compounds in a comparative sense. This kind of analysis can give rise to few numbers of potential compounds from hundreds, whom can further be screened through in vitro and in vivo studies, and human trails leading to the drug development. Methods: Phytochemicals along with their potential antidiabetic property were classified according to their basic chemical skeleton. The chemical structures of all the compounds with antidiabetic activities were elucidated in the present review. In addition to this, the distribution and their other remarkable pharmacological activities of each species is also included. Results: The scrutiny of literature led to identification of 44 plants with antidiabetic compounds (70) and other pharmacological activities. For the sake of information, the distribution of each species in the world is given. Many plant derivatives may exert antidiabetic properties by improving or mimicking the insulin production or action. Different classes of compounds including sulfur compounds (1-4), alkaloids (5-11), phenolic compounds (12-17), tannins (18-23), phenylpropanoids (24-27), xanthanoids (28-31), amino acid (32), stilbenoid (33), benzofuran (34), coumarin (35), flavonoids (36-49) and terpenoids (50-70) were found to be active potential compounds for antidiabetic activity. Of the 70 listed compounds, majorly 17 compounds are from triterpenoids, 13 flavonoids and 7 are from alkaloids. Among all the 44 plant species, maximum number (7) of compounds are reported from Lagerstroemia speciosa followed by Momordica charantia (6) and S. oblonga with 5 compounds. Conclusion: This is the first paper to summarize the established chemical structures of phytochemicals that have been successfully screened for antidiabetic potential and their mechanisms of inhibition. The reported compounds could be considered as potential lead molecules for the treatment of type-2 diabetes. Further, molecular and clinical trials are required to select and establish the therapeutic drug candidates.


Author(s):  
Roohi Mohi-ud-din ◽  
Reyaz Hassan Mir ◽  
Prince Ahad Mir ◽  
Saeema Farooq ◽  
Syed Naiem Raza ◽  
...  

Background: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. Objective: The present review is focussed to summarize and collect the updated review of information of Genus Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. Conclusion: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory both in vitro & in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.


2019 ◽  
Vol 22 (8) ◽  
pp. 509-520
Author(s):  
Cauê B. Scarim ◽  
Chung M. Chin

Background: In recent years, there has been an improvement in the in vitro and in vivo methodology for the screening of anti-chagasic compounds. Millions of compounds can now have their activity evaluated (in large compound libraries) by means of high throughput in vitro screening assays. Objective: Current approaches to drug discovery for Chagas disease. Method: This review article examines the contribution of these methodological advances in medicinal chemistry in the last four years, focusing on Trypanosoma cruzi infection, obtained from the PubMed, Web of Science, and Scopus databases. Results: Here, we have shown that the promise is increasing each year for more lead compounds for the development of a new drug against Chagas disease. Conclusion: There is increased optimism among those working with the objective to find new drug candidates for optimal treatments against Chagas disease.


2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.


Sign in / Sign up

Export Citation Format

Share Document