Heterocyclization of Thiophenes Derived from Estrone Followed by Cytotoxic, HTRF Kinase and Pim-1 Kinase Evaluations

2019 ◽  
Vol 18 (12) ◽  
pp. 1711-1728 ◽  
Author(s):  
Mahmoud A. Abdelaziz Mahmoud ◽  
Rafat M. Mohareb ◽  
Meshari. A. Al-Sharif
Keyword(s):  
Structural Features ◽  
Pharmacological Activities ◽  
Steroid Nucleus ◽  
Kinase C ◽  
Structure Activity ◽  
Wide Range ◽  
Thiophene Derivatives ◽  
Therapeutic Activities ◽  
Derivatives Of ◽  
Steroidal Derivatives

Background: A wide range of heterocyclic steroidal derivatives gained a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the steroid nucleus are known in the market. Objective: Our main aim of this work was to synthesise a series of heterocyclic compounds especially thiophene and thienopyridine derivatives containing the estrone nucleus. The synthesized compounds posses antitumor and kinases inhibitions. Method: Thiophene derivatives of estrone were synthesized and used for further heterocyclization reactions through the reaction with the different reagent. Results: Antiproliferative evaluations and c-Met kinase, Pim-1 kinase inhibitions were performed where some compounds revealed high activities. Conclusion: Compounds that showed high antiproliferative activity and c-Met- kinase inhibitions were tested for all compounds. The most promising compounds 3b, 5c, 6c, 8d, 8f, 13e, 13f, 18b and 20d were further investigated against tyrosine kinase (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Compounds 6b, 13b, 16b and 16c were selected to examine their Pim-1 kinase inhibition activity where compounds 11c, 18b and 20f showed high activities. Structure-Activity Relationship (SAR) was rationalized by looking at the varying structural features of the molecules.

scholarly journals Synthetic Chiral Derivatives of Xanthones: Biological Activities and Enantioselectivity Studies

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 791 ◽  
Author(s):  
Carla Fernandes ◽  
Maria Carraro ◽  
João Ribeiro ◽  
Joana Araújo ◽  
Maria Tiritan ◽  
...  
Keyword(s):  
Biological Activity ◽  
Biological Activities ◽  
Pharmacological Activities ◽  
Sar Studies ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Wide Range ◽  
Synthetic Methodologies ◽  
Derivatives Of ◽  
Biological And Pharmacological Activities

Many naturally occurring xanthones are chiral and present a wide range of biological and pharmacological activities. Some of them have been exhaustively studied and subsequently, obtained by synthesis. In order to obtain libraries of compounds for structure activity relationship (SAR) studies as well as to improve the biological activity, new bioactive analogues and derivatives inspired in natural prototypes were synthetized. Bioactive natural xanthones compromise a large structural multiplicity of compounds, including a diversity of chiral derivatives. Thus, recently an exponential interest in synthetic chiral derivatives of xanthones (CDXs) has been witnessed. The synthetic methodologies can afford structures that otherwise could not be reached within the natural products for biological activity and SAR studies. Another reason that justifies this trend is that both enantiomers can be obtained by using appropriate synthetic pathways, allowing the possibility to perform enantioselectivity studies. In this work, a literature review of synthetic CDXs is presented. The structures, the approaches used for their synthesis and the biological activities are described, emphasizing the enantioselectivity studies.

Pharmacologic activities of 5, 6-Diaryl/heteroaryl-3-substituted-1, 2, 4-triazines as a privileged scaffold in drug development

2021 ◽  
Vol 21 ◽  
Author(s):  
Zahra Zakeri Khatir ◽  
Hamid Irannejad
Keyword(s):  
Biological Data ◽  
Pharmacological Activities ◽  
Drug Candidates ◽  
Structure Activity ◽  
Wide Range ◽  
Privileged Structure ◽  
Triazine Derivatives ◽  
Privileged Scaffold ◽  
Substituted 1 ◽  
Anti Hiv

: 1, 2, 4-Triazine derivatives have received much attention due to their multifunctional nature, especially in diverse pharmacological properties as well as a key fragment in many drug candidates. Introduction of a vicinal 5, 6-diaryl/heteroaryl moiety on the 1, 2, 4-triazine ring has attracted plentiful attention in the field of medicinal chemistry. 5, 6-Diaryl/heteroaryl-3-substituted-1, 2, 4-triazine is as a prominent scaffold in many drug candidates which has shown a wide range of pharmacological activities such as anti-diabetic, antifungal, anti-inflammatory, anticancer, anti-HIV, neuroprotective, anticonvulsant, anti- Alzheimer, anti-Parkinson and antioxidant. In this review, we have discussed synthesis, various pharmacological activities of 5, 6-diaryl/heteroaryl-3-substituted-1, 2, 4-triazines, their structure-activity relationship (SAR), pharmacophoric elements and their mechanism of action reported in the published articles during 2000-2019. Evaluation of compounds by PAINS filtering tool was accomplished and showed that this versatile structure could be considered as a privileged structure. Compilation of the biological data confirmed that the position 3 of the 1,2,4-triazine is a key location to determine the affinity and selectivity of the 5,6-diaryl/heteroaryl-3-substituted-1, 2, 4-triazines towards different biologic targets. Specific geometrical and thermodynamic characters of this motif have prompted it as a frequent hitter.

scholarly journals Structure–Activity Relationship of Phytotoxic Natural 10-Membered Lactones and Their Semisynthetic Derivatives

2021 ◽  
Vol 7 (10) ◽  
pp. 829
Author(s):  
Anna Dalinova ◽  
Anatoly Fedorov ◽  
Vsevolod Dubovik ◽  
Olga Voitsekhovskaja ◽  
Elena Tyutereva ◽  
...  
Keyword(s):  
Rational Design ◽  
Fungicidal Activity ◽  
Structural Features ◽  
Hydroxyl Group ◽  
High Yield ◽  
Sf9 Cells ◽  
Structure Activity ◽  
Relationship Of ◽  
Derivatives Of ◽  
Target Activity

Ten-membered lactones (nonenolides) demonstrate phytotoxic, antimicrobial, and fungicidal activity promising for the development of natural product-derived pesticides. The fungus Stagonospora cirsii is able to produce phytotoxic stagonolides A (1), J (2), K (3) and herbarumin I (4) with high yield. The aim of this study was to create a set of structurally related nonenolides and to reveal the structural features that affect their biological activity. Stagonolide A (1) and C-7 oxidized stagonolide K (11) showed the highest phytotoxicity in leaf puncture assay and agar seedlings assay. The oxidation of C-7 hydroxyl group (as in 1, acetylstagonolide A (10) and (11) led to the manifestation of toxicity to microalgae, Bacillus subtilis and Sf9 cells regardless of the configuration of C-9 propyl chains (R in 1 and 10, S in 11). C-7 non-oxidized nonenolides displayed none or little non-target activity. Notably, 7S compounds were more phytotoxic than their 7R analogues. Due to the high inhibitory activity against seedling growth and the lack of side toxicity, mono- and bis(acetyl)- derivatives of herbarumin I were shown to be potent for the development of pre-emergent herbicides. The identified structural features can be used for the rational design of new herbicides.

scholarly journals An Overview of Bioactive Alkaloid, Semi-Synthetic Analogs, Mechanism of Action and Structure-Activity Relationship of Piperine as Antioxidant

2021 ◽  
Vol 33 (9) ◽  
pp. 2244-2250
Author(s):  
Sagar Joshi ◽  
Salahuddin ◽  
Rajnish Kumar ◽  
Divya Sharma
Keyword(s):  
Antioxidant Activity ◽  
Mechanism Of Action ◽  
Structure Activity Relationship ◽  
Black Pepper ◽  
Activity Relationship ◽  
Pharmacological Activities ◽  
Structure Activity ◽  
Natural Alkaloid ◽  
Relationship Of ◽  
Derivatives Of

Piperine, a natural alkaloid obtained from black pepper exhibit a variety of pharmacological activities like antioxidant activity and in this article, the mechanism of the antioxidant, structure-activity relationship of piperine as an antioxidant and various schemes of derivatives of piperine as antioxidants were discussed.

Vitex Diterpenoids: Structural Diversity and Pharmacological Activity

2020 ◽  
Vol 26 (1) ◽  
pp. 138-159 ◽  
Author(s):  
Yanfei Ban ◽  
Tianshuang Xia ◽  
Rui Jing ◽  
Yaoli Guo ◽  
Yiya Geng ◽  
...  
Keyword(s):  
Pharmacological Activity ◽  
Hormone Level ◽  
Biological Activities ◽  
Folk Medicine ◽  
Structural Diversity ◽  
Pharmacological Activities ◽  
Structure Activity ◽  
Wide Range ◽  
Potential Applications

Plants of the genus Vitex (Verbenaceae) are mainly distributed throughout tropical and temperate regions, and many Vitex plants have been traditionally used in folk medicine. Plants of this genus are a rich source of diterpenoids, which not only displayed versatile structural diversity with potential chemotaxonomical significance but also exhibited a wide range of biological activities, mainly including in vitro cytotoxic, antiinflammatory, antimicrobial, hormone level-regulating and antiangiogenic activities. Recently, a series of bioactive diterpenoids, with interesting carbon skeletons, have been reported and gathered considerable interest. This article systematically reviewed diterpenoids isolated from the genus Vitex that appeared in the literature up to December 2018, critically highlighting their structural diversity and pharmacological activities. Up to now, a total of 154 diterpenoids with diverse structures have been isolated and identified from Vitex plants. The authors also summarized the reported structure-activity relationships of those well explored Vitex diterpenoids. Finally, the authors discussed the challenges and potential applications of these diterpenoids in the future.

scholarly journals Review Article: Various Biological Activities of Coumarin and Oxadiazole Derivatives.

2017 ◽  
Vol 10 (7) ◽  
pp. 38 ◽  
Author(s):  
Sunny Jalhan
Keyword(s):  
Biological Activities ◽  
Biochemical Properties ◽  
Review Article ◽  
Pharmacological Activities ◽  
Wide Range ◽  
Methylene Groups ◽  
Anti Oxidant ◽  
Oxadiazole Derivatives ◽  
Anti Inflammatory ◽  
Derivatives Of

In this review article data is collected regarding the various derivatives of coumarin and oxadiazole as both these have wide range of biological activities and they can be further modified to synthesize more effective and potent drugs. Coumarin class of organic compounds consists of 1,2-benzopyrone ring system as a basic parent scaffold. These benzopyrones are subdivided into alpha-benzopyrones and gamma benzopyrones; with coumarin class of compounds belonging to alpha-benzopyrones. Since the last few years, coumarins were synthesized in many of their derivative forms. Their pharmacological, therapeutic and biochemical properties depend upon their pattern of substitution. Coumarins exhibit a wide range of pharmacological activities, which includes anti-diabetic, anti-viral, anti-microbial, anticancer, anti-oxidant, anti-parasitic, anti-helminthic, anti-proliferative, anti-convulsant, anti-inflammatory and antihypertensive activities. 1,3,4-Oxadiazole is a heterocyclic compound containing an oxygen atom and two nitrogen atoms in a five-membered ring. It is derived from furan by substitution of two methylene groups (=CH) with two pyridine type nitrogens (-N=). There are three known isomers: 1,2,4-oxadiazole, 1,2,3-oxadiazole and 1,2,5- oxadiazole. Oxadiazole moiety shows antimicrobial, anticancer and anti-inflammatory activity and suitably substituted 1,3,4-oxadiazole having biological activities like antimicrobial, anticancer and other biological activities.

scholarly journals Euphorbia Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5055
Author(s):  
Douglas Kemboi ◽  
Xavier Siwe-Noundou ◽  
Rui W. M. Krause ◽  
Moses K. Langat ◽  
Vuyelwa Jacqueline Tembu
Keyword(s):  
Drug Discovery ◽  
Structural Diversity ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Hydroxyl Group ◽  
Pharmacological Activities ◽  
Structure Activity ◽  
Wide Range ◽  
Ic50 Values

Euphorbia species have a rich history of ethnomedicinal use and ethnopharmacological applications in drug discovery. This is due to the presence of a wide range of diterpenes exhibiting great structural diversity and pharmacological activities. As a result, Euphorbia diterpenes have remained the focus of drug discovery investigations from natural products. The current review documents over 350 diterpenes, isolated from Euphorbia species, their structures, classification, biosynthetic pathways, and their structure–activity relationships for the period covering 2013–2020. Among the isolated diterpenes, over 20 skeletal structures were identified. Lathyrane, jatrophane, ingenane, ingenol, and ingol were identified as the major diterpenes in most Euphorbia species. Most of the isolated diterpenes were evaluated for their cytotoxicity activities, multidrug resistance abilities, and inhibitory activities in vitro, and reported good activities with significant half-inhibitory concentration (IC50) values ranging from 10–50 µM. The lathyranes, isopimaranes, and jatrophanes diterpenes were further found to show potent inhibition of P-glycoprotein, which is known to confer drug resistance abilities in cells leading to decreased cytotoxic effects. Structure–activity relationship (SAR) studies revealed the significance of a free hydroxyl group at position C-3 in enhancing the anticancer and anti-inflammatory activities and the negative effect it has in position C-2. Esterification of this functionality, in selected diterpenes, was found to enhance these activities. Thus, Euphorbia diterpenes offer a valuable source of lead compounds that could be investigated further as potential candidates for drug discovery.

scholarly journals RECENT DEVELOPMENTS AND MULTIPLE BIOLOGICAL ACTIVITIES AVAILABLE WITH 1, 8-NAPHTHYRIDINE DERIVATIVES: A REVIEW

2019 ◽  
pp. 17-37
Author(s):  
Vinod Kumar Gurjar ◽  
Dilipkumar Pal
Keyword(s):  
Biological Activities ◽  
Neurological Diseases ◽  
Growth Factor Receptor ◽  
Pharmaceutical Chemistry ◽  
Pharmacological Activities ◽  
Egfr Inhibition ◽  
Wide Range ◽  
Versatile Tool ◽  
Recent Developments ◽  
Derivatives Of

Within the wide range of nitrogen-containing heterocyclic compounds, the derivatives of 1,8-naphthyridine (NPTR) have gained a rising interest due to their reported versatile biological activities. The derivatives of NPTR scaffold are found to invite special interest from researchers nowadays on the significance of their manifestations of multiple attractive pharmacological activities which establish them as an effective and versatile tool in pharmaceutical chemistry and drug discovery. The diverse biological activities mainly include anti-inflammatory, antimicrobial, antiviral, anticancer, antihypertensive and analgesic activities. Novel NPTR scaffold has emerged its potency to treat neurological diseases like depression and Alzheimer's disease. Further these agents possess different inhibitory activities, such as anti-HIV, anti-osteoporotic, αvβ3 antagonism, antimalarial, platelet aggregation, anti-oxidant, anti-allergic, gastric antisecretory, anticonvulsant, epidermal growth factor receptor (EGFR) inhibition, protein kinase inhibition, ionotropic properties, β3 antagonism, phosphodiesterase 4 (PDE 4) inhibitions, adenosine receptor agonistic activity, adrenoceptors antagonism and DNA stabilizing activity, etc. In this review, we highlight the updates of different 1,8-naphthyridine derivatives and explain the key data available in the context of various biological activities of NPTR derivatives available from the literature. This may direct opportunity in researches in the synthesis of novel medicinal agents and the development of new heterocycles for modification of existing biological actions as well as evaluation of other possible pharmacological activities.

Uses of Cyclohexan-1,3-dione for the Synthesis of Thiazole, Pyrazole, Thiophene, Isoxazole and Pyran Derivatives with Antitumor Activities

2020 ◽  
Vol 17 (5) ◽  
pp. 597-609
Author(s):  
Rafat Milad Mohareb ◽  
Nadia Youssef Megally Abdo ◽  
Waleed Nabeel Al-darkazali
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Cancer Cell Lines ◽  
Structural Features ◽  
Active Compounds ◽  
Wide Range ◽  
Heterocyclic Derivatives ◽  
Therapeutic Activities ◽  
High Inhibition

Background: A wide range of thiazole, pyrazole and pyran derivatives gained special attention due to pharmacological activities especially therapeutic activities. Many pharmacological drugs containing the thiazole and pyrazole nuclei are known in the market. Methods: The 2-arylidencyclohexan-1,3-dione 3a-c were the key starting compounds for many heterocyclic reactions to produce substituted heterocyclic derivatives. Results: Antiproliferative activities of the produced compounds against six cancer cell lines A549, HT-29, MKN-45, U87MG, SMMC-7721 and H460 were measured in which the compounds showed high inhibition. The most promising compounds were tested against tyrosine kinases (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Structure-Activity Relationship (SAR) was rationalized by assessing the varying structural features of the molecules. In addition, the most active compounds were selected for Pim-1 inhibition. Conclusion: Thirty compounds were synthesized. Ten of them (3a, 3c, 5a, 5c, 7a, 10f, 11a, 13c, 16a and 16c) were the most active compounds for selected cancer cell lines. Compounds 3c, 5c, 7a, 10f, 13c and 16c showed high inhibition toward the tyrosine kinases while compounds 3c, 5c and 10f were the most potent to inhibit Pim-1.

Synthesis of Thiazole, Thiophene, Pyran and Pyridine Derivatives Derived from 3-phenyl-1H-pyrazol-5(4H)-one with Anti-proliferative, Tyrosine Kinase and PIM-1 Kinase Inhibitions

2020 ◽  
Vol 17 (4) ◽  
pp. 485-501
Author(s):  
Rafat Milad Mohareb ◽  
Ibram Refat Mikhail
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Cancer Cell Lines ◽  
Structural Features ◽  
Pyrazole Derivatives ◽  
Active Compounds ◽  
Starting Compound ◽  
Wide Range ◽  
Therapeutic Activities

Background: A wide range of pyrazole derivatives gained special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the pyrazole nucleus are known in the market. Methods: The 3-phenyl-1H-pyrazol-5(4H)-one was the key starting compound for many heterocyclic reactions to produce substituted and fused pyrazole derivatives. Results: Antiproliferative activities of the produced compounds against six cancer cell lines A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460 were measured through which compounds showed high inhibitions. The most promising compounds were tested against tyrosine kinases (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Structure-Activity Relationship (SAR) was rationalized by looking at the varying structural features of the molecules. In addition, the most active compounds were selected for Pim-1 inhibition. Conclusion: Thirty-nine pyrazole derivatives were synthesized. Nine of them 8b, 9, 12b, 12d, 14b, 15b, 18d, 18f, 19b, and 21d were the most active compounds toward the selected cancer cell lines. Compounds 12b, 14b, 18d, 18f, and 21d showed high inhibitions toward the tyrosine kinases, whereas compounds 14b, 18d, and 18f were the most potent inhibitors of Pim-1.

Sign in / Sign up

Export Citation Format

Share Document