Indole derivatives (2010–2020) as versatile tubulin inhibitors: synthesis and structure–activity relationships

2021 ◽  
Vol 13 (20) ◽  
pp. 1795-1828
Author(s):  
Fatima Naaz ◽  
Kumari Neha ◽  
Md Rafi Haider ◽  
Syed Shafi
Keyword(s):  
Cancer Therapy ◽  
Present Article ◽  
Dynamic Equilibrium ◽  
Biological Activities ◽  
Indole Derivatives ◽  
Tubulin Inhibitors ◽  
Structure Activity Relationships ◽  
Drug Candidates ◽  
Structure Activity ◽  
Wide Range

Tubulin inhibitors are conjugates that interfere with the dynamic equilibrium of the polymerization and depolymerization of microtubules. Among all the reported conjugates, indole moiety is one of the most significant classes for the development of new drug candidates for cancer therapy. Due to their presence in a wide range of natural as well as synthetic antitubulin agents, indole has become a versatile scaffold in research, and various synthetic and semisynthetic indole-based antitubulin agents have been identified and reported. The present article focuses on the reported indole-based tubulin inhibitors of synthetic origin from last the decade. Synthesis, structure–activity relationships and biological activities of synthetic indole derivatives along with brief updates on their antitubulin activity are presented.

Medicinal applications of coumarins bearing azetidinone and thiazolidinone moieties

2021 ◽  
Author(s):  
Siddappa A Patil ◽  
Shivaputra A Patil ◽  
Temilade Fariyike ◽  
Kostiantyn O Marichev ◽  
Hector Mario Heras Martinez ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Biological Activities ◽  
Heterocyclic Ring ◽  
Pharmacological Properties ◽  
Structure Activity Relationships ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Wide Range ◽  
Synthetic Routes ◽  
Synthetic Methodologies

Coumarins (2 H-chromen-2-ones), also known as benzopyran-2-ones, are a family of naturally occurring heterocyclic ring systems that contain a lactone moiety. Coumarins exhibit a wide range of well-studied pharmacological properties. Over the last few decades, as a result of advances in diverse oriented synthetic routes, physicochemical properties and numerous biological activities, coumarins have become globally studied molecules from various synthetic and medicinal chemists. Recently, several bioactive coumarins bearing azetidinone and thiazolidinone moieties have been found to display a range of therapeutic characteristics, including antimicrobial, anticancer, antidiabetic and anti-inflammatory properties. This review offers a brief description of the synthetic methodologies, known bioactivity and structure–activity relationships of coumarins bearing azetidinones and thiazolidinones.

Isothiocyanate Synthetic Analogs: Biological Activities, Structure-Activity Relationships and Synthetic Strategies

2014 ◽  
Vol 14 (12) ◽  
pp. 963-977 ◽  
Author(s):  
Andrea Milelli ◽  
Carmela Fimognari ◽  
Nicole Ticchi ◽  
Paolo Neviani ◽  
Anna Minarini ◽  
...  
Keyword(s):  
Biological Activities ◽  
Synthetic Analogs ◽  
Structure Activity Relationships ◽  
Structure Activity

scholarly journals Modern Synthetic Methods for the Stereoselective Construction of 1,3-Dienes

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 249
Author(s):  
Raquel G. Soengas ◽  
Humberto Rodríguez-Solla
Keyword(s):  
Organic Chemistry ◽  
Natural Products ◽  
Functional Group ◽  
Biological Activities ◽  
Synthetic Methods ◽  
Bond Forming ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

The 1,3-butadiene motif is widely found in many natural products and drug candidates with relevant biological activities. Moreover, dienes are important targets for synthetic chemists, due to their ability to give access to a wide range of functional group transformations, including a broad range of C-C bond-forming processes. Therefore, the stereoselective preparation of dienes have attracted much attention over the past decades, and the search for new synthetic protocols continues unabated. The aim of this review is to give an overview of the diverse methodologies that have emerged in the last decade, with a focus on the synthetic processes that meet the requirements of efficiency and sustainability of modern organic chemistry.

Improved synthesis of 4-/6-substituted 2-carboxy-1H-indole-3-propionic acid derivatives and structure–activity relationships as GPR17 agonists

MedChemComm ◽  
2014 ◽  
Vol 5 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Younis Baqi ◽  
Samer Alshaibani ◽  
Kirsten Ritter ◽  
Aliaa Abdelrahman ◽  
Andreas Spinrath ◽  
...  
Keyword(s):  
Propionic Acid ◽  
Indole Derivatives ◽  
Structure Activity Relationships ◽  
Structure Activity

Several tri- and tetra-substituted indole derivatives were synthesized and evaluated as human GPR17 agonists. Steep structure–activity relationships were observed.

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.

Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents

2020 ◽  
Vol 44 (6) ◽  
pp. 2247-2255
Author(s):  
Qifan Zhou ◽  
Lina Jia ◽  
Fangyu Du ◽  
Xiaoyu Dong ◽  
Wanyu Sun ◽  
...  
Keyword(s):  
Biological Activity ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Activity Assay ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Enhancer Of Zeste

A novel series of pyrrole-3-carboxamides targeting EZH2 have been designed and synthesized. The structure–activity relationships were summarized by combining with in vitro biological activity assay and docking results.

scholarly journals Hybrid cis-stilbene Molecules: Novel Anticancer Agents

2019 ◽  
Vol 20 (6) ◽  
pp. 1300 ◽  
Author(s):  
Natalia Piekuś-Słomka ◽  
Renata Mikstacka ◽  
Joanna Ronowicz ◽  
Stanisław Sobiak
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Distinct Group ◽  
Design Synthesis ◽  
Drug Candidates ◽  
Structure Activity ◽  
Polymerization Inhibitor ◽  
Hybrid Molecules ◽  
Tubulin Polymerization Inhibitor ◽  
Pharmacologically Active

The growing interest in anticancer hybrids in the last few years has resulted in a great number of reports on hybrid design, synthesis and bioevaluation. Many novel multi-target-directed drug candidates were synthesized, and their biological activities were evaluated. For the design of anticancer hybrid compounds, the molecules of stilbenes, aromatic quinones, and heterocycles (benzimidazole, imidazole, pyrimidine, pyridine, pyrazole, quinoline, quinazoline) were applied. A distinct group of hybrids comprises the molecules built with natural compounds: Resveratrol, curcumin, coumarin, and oleanolic acid. In this review, we present the studies on bioactive hybrid molecules of a well-known tubulin polymerization inhibitor, combretastatin A-4 and its analogs with other pharmacologically active entities. The mechanism of anticancer activity of selected hybrids is discussed considering the structure-activity relationship.

scholarly journals Structure-Activity Relationships for the Anaesthetic and Analgaesic Properties of Aromatic Ring-Substituted Ketamine Esters

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2950
Author(s):  
Ivaylo V. Dimitrov ◽  
Martyn G. Harvey ◽  
Logan J. Voss ◽  
James W. Sleigh ◽  
Michael J. Bickerdike ◽  
...  
Keyword(s):  
Electronic Properties ◽  
Benzene Ring ◽  
Aromatic Ring ◽  
Alkyl Esters ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Wide Range ◽  
Powerful Electron ◽  
Electron Withdrawing Substituents

A series of benzene ring substituted ketamine N-alkyl esters were prepared from the corresponding substituted norketamines. Few of the latter have been reported since they have not been generally accessible via known routes. We report a new general route to many of these norketamines via the Neber (oxime to α-aminoketone) rearrangement of readily available substituted 2-phenycyclohexanones. We explored the use of the substituents Cl, Me, OMe, CF3, and OCF3, with a wide range of lipophilic and electronic properties, at all available benzene ring positions. The 2- and 3-substituted compounds were generally more active than 4-substituted compounds. The most generally acceptable substituent was Cl, while the powerful electron-withdrawing substituents CF3 and OCF3 provided fewer effective analogues.

scholarly journals A Comprehensive QSAR Study on Antileishmanial and Antitrypanosomal Cinnamate Ester Analogues

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4358 ◽  
Author(s):  
Freddy A. Bernal ◽  
Thomas J. Schmidt
Keyword(s):  
Biological Activities ◽  
Strong Dependence ◽  
Health Improvement ◽  
Underlying Structure ◽  
Parasitic Infections ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Antitrypanosomal Activity ◽  
Validation Parameters ◽  
Test Sets

Parasitic infections like leishmaniasis and trypanosomiasis remain as a worldwide concern to public health. Improvement of the currently available drug discovery pipelines for those diseases is therefore mandatory. We have recently reported on the antileishmanial and antitrypanosomal activity of a set of cinnamate esters where we identified several compounds with interesting activity against L. donovani and T. brucei rhodesiense. For a better understanding of such compounds’ anti-infective activity, analyses of the underlying structure-activity relationships, especially from a quantitative point of view, would be a prerequisite for rational further development of such compounds. Thus, quantitative structure-activity relationships (QSAR) modeling for the mentioned set of compounds and their antileishmanial and antitrypanosomal activity was performed using a genetic algorithm as main variable selection tool and multiple linear regression as statistical analysis. Changes in the composition of the training/test sets were evaluated (two randomly selected and one by Kennard-Stone algorithm). The effect of the size of the models (number of descriptors) was also investigated. The quality of all resulting models was assessed by a variety of validation parameters. The models were ranked by newly introduced scoring functions accounting for the fulfillment of each of the validation criteria evaluated. The test sets were effectively within the applicability domain of the best models, which demonstrated high robustness. Detailed analysis of the molecular descriptors involved in those models revealed strong dependence of activity on the number and type of polar atoms, which affect the hydrophobic/hydrophilic properties causing a prominent influence on the investigated biological activities.

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