scholarly journals Anticancer Activity of Natural and Synthetic Chalcones

2021 ◽  
Vol 22 (21) ◽  
pp. 11306
Author(s):  
Teodora Constantinescu ◽  
Claudiu N. Lungu
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Basic Structure ◽  
Anticancer Therapy ◽  
Huge Number ◽  
Current Standard ◽  
Aromatic Residues ◽  
Diaryl Ether ◽  
Hybrid Molecules

Cancer is a condition caused by many mechanisms (genetic, immune, oxidation, and inflammatory). Anticancer therapy aims to destroy or stop the growth of cancer cells. Resistance to treatment is theleading cause of the inefficiency of current standard therapies. Targeted therapies are the most effective due to the low number of side effects and low resistance. Among the small molecule natural compounds, flavonoids are of particular interest for theidentification of new anticancer agents. Chalcones are precursors to all flavonoids and have many biological activities. The anticancer activity of chalcones is due to the ability of these compounds to act on many targets. Natural chalcones, such as licochalcones, xanthohumol (XN), panduretin (PA), and loncocarpine, have been extensively studied and modulated. Modification of the basic structure of chalcones in order to obtain compounds with superior cytotoxic properties has been performed by modulating the aromatic residues, replacing aromatic residues with heterocycles, and obtaining hybrid molecules. A huge number of chalcone derivatives with residues such as diaryl ether, sulfonamide, and amine have been obtained, their presence being favorable for anticancer activity. Modification of the amino group in the structure of aminochalconesis always favorable for antitumor activity. This is why hybrid molecules of chalcones with different nitrogen hetercycles in the molecule have been obtained. From these, azoles (imidazole, oxazoles, tetrazoles, thiazoles, 1,2,3-triazoles, and 1,2,4-triazoles) are of particular importance for the identification of new anticancer agents.

Arylhydrazono/Aryldiazenyl Pyrazoles: Green One-Pot Solvent-Free Synthesis and Anticancer Evaluation

2020 ◽  
Vol 17 (10) ◽  
pp. 772-778
Author(s):  
Abdulrhman Alsayari ◽  
Abdullatif Bin Muhsinah ◽  
Yahya I. Asiri ◽  
Jaber Abdullah Alshehri ◽  
Yahia N. Mabkhot ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Binding Mode ◽  
Docking Studies ◽  
Solvent Free ◽  
Pyrazole Derivatives ◽  
One Pot ◽  
Solvent Free Conditions ◽  
Hybrid Molecules

The aim of this study was to synthesize and evaluate the biological activity of pyrazole derivatives, in particular, to perform a “greener” one-pot synthesis using a solvent-free method as an alternative strategy for synthesizing hydrazono/diazenyl-pyridine-pyrazole hybrid molecules with potential anticancer activity. Effective treatment for all types of cancers is still a long way in the future due to the severe adverse drug reactions and drug resistance associated with current drugs. Therefore, there is a pressing need to develop safer and more effective anticancer agents. In this context, some hybrid analogues containing the bioactive pharmacophores viz. pyrazole, pyridine, and diazo scaffolds were synthesized by one-pot method. Herein, we describe the expedient synthesis of pyrazoles by a onepot three-component condensation of ethyl acetoacetate/acetylacetone, isoniazid, and arenediazonium salts under solvent-free conditions, and the evaluation of their cytotoxicity using a sulforhodamine B assay on three cancer cell lines. Molecular docking studies employing tyrosine kinase were also carried out to evaluate the binding mode of the pyrazole derivatives under study. 1-(4-Pyridinylcarbonyl)-3- methyl-4-(2-arylhydrazono)-2-pyrazolin-5-ones and [4-(2-aryldiazenyl)-3,5-dimethyl-1H-pyrazol-1- yl]-4-pyridinylmethanones, previously described, were prepared using an improved procedure. Among these ten products, 1-isonicotinoyl-3-methyl-4-[2-(4-nitrophenyl)hydrazono]-2-pyrazolin-5-one (1f) displayed promising anticancer activity against the MCF-7, HepG2 and HCT-116 cell lines, with an IC50 value in the range of 0.2-3.4 μM. In summary, our findings suggest that pyrazoles containing hydrazono/ diazenyl and pyridine pharmacophores constitute promising scaffolds for the development of new anticancer agents.

Development and Advances of Drugs for Cancer Theranostics – PART-IV

2021 ◽  
Vol 21 (18) ◽  
pp. 1644-1644
Author(s):  
Lian-Shun Feng
Keyword(s):  
Drug Discovery ◽  
Side Effects ◽  
Anticancer Activity ◽  
Anticancer Drug ◽  
Anticancer Agents ◽  
Drug Repurposing ◽  
Biological Properties ◽  
Drug Candidates ◽  
Pharmacokinetic Profiles ◽  
Hybrid Molecules

Cancer, a highly heterogeneous disease at intra/inter patient levels, is one of the most serious threats to human health across the world [1, 2]. Notwithstanding the noteworthy advances in its treat-ment, the morbidity and mortality of cancer are projected to grow for a long period, and the global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020 [3]. Accordingly, there is a constant need to explore novel anticancer agents. <p> There are several strategies to discover novel anticancer candidates: (1) new lead hits or candidates from natural resources [4] whichexhibit various biological properties and are a rich source of com-pounds in drug discovery due to the structural and mechanistic diversity, and more than 60% anti-cancer agents can be traced to a natural product; (2) Molecular hybridization is one of the most prom-ising strategies for the discovery of novel anticancer drug candidates since hybrid molecules have the potential to bind multiple targets or to enhance the effect through acting with another bio-target or to counterbalance the side effects caused by the other part of the hybrid [5]; (3) Dimerization is a useful tool to develop novel anticancer drug candidates with enhanced biological activity, reduced side effects and improved pharmacokinetic profiles [6]; (4) Drug repurposing strategy is is an attractive strategy and has been approved, along with non-anticancer macrolide drugs for the treatment of cancer, for anticancer drug discovery since toxicity and pharmacokinetic profiles have already been estab-lished [7]. <p> Heterocycles coumarin, β-lactone, macrolide and triazole are useful anticancer pharmacophores since their derivatives could exert the anticancer activity through diverse mechanisms, inclusive of inhibition of aromatase, carbonic anhydrase, ki-nase, P-glycoprotein, sulfatase, telomerase, vascular endothelial growth factor receptor 2 and tubulin [8-11]. In particular, nat-ural-derived coumarin, β-lactone and macrolide derivatives are important sources of new anticancer lead hits/candidates; mac-rolide repurposed drugs can circumvent high cost and long-time associated with traditional drug discovery strategies; couma-rin, β-lactone and macrolide hybrids as well as bis-triazole compounds have the potential to enhance the anticancer activity, overcome drug resistance, reduce the side effects and improve pharmacokinetic profiles.

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.

Chemistry and Anticancer Activity of Hybrid Molecules and Derivatives Based on 5-Fluorouracil

2021 ◽  
Vol 28 ◽  
Author(s):  
Wilson Cardona-G ◽  
Angie Herrera-R ◽  
Wilson Castrillón-L ◽  
Howard Ramírez-Malule
Keyword(s):  
Side Effects ◽  
Anticancer Activity ◽  
Antitumor Agents ◽  
Biological Activities ◽  
Hybrid Molecule ◽  
Drug Discovery And Development ◽  
Promising Strategy ◽  
Structure Activity ◽  
Hybrid Molecules ◽  
Sar Analysis

: Cancer still continues as an important cause of death worldwide. Thus, several conventional anticancer treatments are widely used, however, most of them display low selectivity against malignant cells and induce many adverse side effects. Among these, the use of therapies based on 5-Fluorouracil (5-FU) has been one of the most efficient, with a broad-spectrum. Due to these circumstances, various modifications of 5-FU have been developed to improve drug delivery and reduce side effects. Among the optimization strategies, modifications of 5-FU at N1 or N3 position are made, usually including incorporation of pharmacological active compounds with anticancer activity (called hybrid molecule) and functionalization with other groups of compounds (called conjugates). Several studies have been conducted in the search for new alternative therapies against cancer, many of them have evidenced that hybrid compounds exhibit good anticancer activity, which has emerged as a promising strategy in this field of drug discovery and development. Furthermore, the binding of 5-FU to amino acids, peptides, phospholipids, polymers, among others, improves metabolic stability and absorption. This review highlights the potential of hybrids and derivatives based on 5-FU as a scaffold for the development of antitumor agents, besides, it also presents a detailed description of the different strategies employed to design and synthesized these compounds, together with their biological activities and Structure-Activity Relationship (SAR) analysis.

Recent Advances in the Development of Pyrazolopyridines as Anticancer Agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Xiaotong Gu ◽  
Shutao Ma
Keyword(s):  
Anticancer Activity ◽  
21St Century ◽  
Malignant Tumor ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Biological Processes ◽  
Health It ◽  
Recent Advances ◽  
New Chemical Entities

: Cancer, especially malignant tumor, is a serious threat to people's life and health. It is recognized as an enormous challenge in the 21st century. Continuous efforts are needed to overcome this problem. Pyrazolopyridine nucleus, similar in structure to purine, shows a variety of biological activities, which is mainly attributed to the antagonistic nature towards the natural purines in many biological processes. This has aroused enormous attention for many researchers. At present, a large number of new chemical entities containing pyrazolopyridine nucleus have been found as anticancer agents. In this review we summarize novel pyrazolopyridine-containing derivatives with biological activities. Furthermore, we outline the relationships between the structures of variously modified pyrazolopyridines and their anticancer activity.

Progress and development of C-3, C-6, and N-9 position substituted carbazole integrated molecular hybrid molecules as potential anticancer agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Pratibha Mehta Luthra ◽  
Nitin Kumar
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Structural Motif ◽  
Hybrid Compounds ◽  
Hybrid Molecules ◽  
Anticancer Mechanism ◽  
Pharmacologically Active

Abstract: The carbazole skeleton, a key structural motif occurring naturally or chemically synthesized, have shown various biological activities. Molecular hybridization based on the combination of two or more bioactive pharmacophores has been an important tool to convert the potent structural leads to form new hybrid compounds with improved biological activity. In recent years, modifications/substitutions of the carbazole motif at C3, C6, N9 position have been carried to develop novel carbazole based potential anticancer agents in the cancer therapy. In the last fifteen years, several compounds based on carbazole core integrated to pharmacologically active molecular hybrid having active pharmacophore such as 1,3,4-thiadiazole, thiazole, guanidine, sulfonamides, glyoxamides, imidazole, phenanthrene, rhodamine, chalcones, imidazopyridine, platinum 2H-chromen-2-one, hydrazones, piperazine, Isoxazole-thiadiazole, pyrazole etc. have been synthesized showing anticancer profile at sub-micromolar to nano-molar concentrations. We have thoroughly reviewed the design, progress and development of C-3, C-6, and N-9 position substituted carbazole derivatives integrated with various medicinally active pharmacophore as potential anticancer agents evaluated against various cancer cell lines. Additionally, the anticancer mechanism and in vivo activity of the reported compounds have been discussed. This study will support in designing of a new pharmacophore that can be linked to carbazole motif for development for new, potent and target specific anticancer drugs with improved pharmacokinetics and minimal side effects.

scholarly journals Design, Synthesis, and In Vitro Evaluation of Novel Indolyl DiHydropyrazole Derivatives as Potential Anticancer Agents

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5235
Author(s):  
Katharigatta N. Venugopala ◽  
Mohammed Habeebuddin ◽  
Bandar E. Aldhubiab ◽  
Afzal Haq Asif
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Structural Features ◽  
Synthetic Methods ◽  
Potential Candidate ◽  
Human Cancer Cell Lines ◽  
Hybrid Molecules

Indoles derived from both natural sources or artificial synthetic methods have been known to interact with aryl hydrocarbon receptors (AhR), and exhibit anticancer activity. In light of these attractive properties, a series of hybrid molecules with structural features of indoles, i.e., those bearing a pyrazoline nucleus, were evaluated for their enhanced anticancer activity. The designed molecules were subjected to molecular docking in order to screen for potential AhR interacting compounds, and the identified indolyl dihydropyrazole derivatives were synthesized. The synthesized compounds were characterized, and their cytotoxicity was evaluated against four human cancer cell lines using the MTT assay. Based on the Glide g-score, H-bonding interactions and bonding energy of 20 candidate molecules were selected for further analysis from the 64 initially designed molecules. These candidate molecules have shown promising anti-proliferative activity against the cell lines tested. Among these candidate molecules, the compounds with hydroxy phenyl substitution on the pyrazoline ring have shown potent activity across all the tested cell lines. The designed scaffold was proven effective for screening potential candidate molecules with anticancer properties, and may be further optimized structurally for yielding the ideal anti-tumorigenic compound for the treatment of various cancers.

Design, Synthesis of novel coumarin conjugated acetamides as promising anticancer agents: An in-silico and in-vitro approach.

2020 ◽  
Vol 20 ◽  
Author(s):  
Mamatha S. V ◽  
S. L. Belagali ◽  
Mahesh Bhat ◽  
Vijay M. Kumbar
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Mtt Assay ◽  
Anticancer Agents ◽  
In Silico ◽  
Active Sites ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Mcf 7

Background: Coumarin and benzophenone possess a vast sphere of biological activities whereas thiazoles display various pharmacological properties. Hence we focused on incorporation of coumarin and thiazole core to the benzophenone skeleton to enhance the bioactivity anticipating their interesting biological properties. Objective: The objective of the current work is synthesis and biological evaluation of a novel series of coumarin fused thiazole derivatives. Methods: A novel series of Coumarin conjugated thiazolyl acetamide hybrid derivatives were synthesized by multistep reaction sequence and were characterized by the FT-IR, LCMS and NMR spectral techniques. The newly synthesized compounds were screened for anticancer activity by in-silico and in-vitro methods. The cytotoxicity of the synthesized unique compounds had been executed for two different cancer cell lines MCF-7 (Breast cancer) and KB (Oral cancer) in comparison with standard paclitaxel by MTT assay. Results: The compound 7f is the potent motif with an acceptable range of IC 50 values for anticancer activity were 63.54 µg/ml and 55.67 µg/ml, against the MCF-7 and KB cell lines, respectively. Molecule docking model revealed that this compound formed three conventional hydrogen bonds with the active sites of the amino acids MET 769, ARG 817 and LYS 721. Conclusion: Compound 7f with two methyl groups on the phenoxy ring and one 4-position methoxy group on the benzoyl ring, showed a significant cytotoxic effect. An advantageous level of low toxicity against normal cell line (L292) by MTT assay was determined.

scholarly journals Molecular Mechanisms of Anticancer Activity of N-Glycosides of Indolocarbazoles LCS-1208 and LCS-1269

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7329
Author(s):  
Roman G. Zenkov ◽  
Olga A. Vlasova ◽  
Varvara P. Maksimova ◽  
Timur I. Fetisov ◽  
Natalia Y. Karpechenko ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Chromatin Remodeling ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Biological Activities ◽  
Binding Constants ◽  
Histone H1 ◽  
Immortalized Cells

Novel indolocarbazole derivatives named LCS were synthesized by our research group. Two of them were selected as the most active anticancer agents in vivo. We studied the mechanisms of anticancer activity in accordance with the previously described effects of indolocarbazoles. Cytotoxicity was estimated by MTT assay. We analyzed LCS-DNA interactions by circular dichroism in cholesteric liquid crystals and fluorescent indicator displacement assay. The effect on the activity of topoisomerases I and II was studied by DNA relaxation assay. Expression of interferon signaling target genes was estimated by RT-PCR. Chromatin remodeling was analyzed–the effect on histone H1 localization and reactivation of epigenetically silenced genes. LCS-induced change in the expression of a wide gene set was counted by means of PCR array. Our study revealed the cytotoxic activity of the compounds against 11 cancer cell lines and it was higher than in immortalized cells. Both compounds bind DNA; binding constants were estimated—LCS-1208 demonstrated higher affinity than LCS-1269; it was shown that LCS-1208 intercalates into DNA that is typical for rebeccamycin derivatives. LCS-1208 also inhibits topoisomerases I and IIα. Being a strong intercalator and topoisomerase inhibitor, LCS-1208 upregulates the expression of interferon-induced genes. In view of LCSs binding to DNA we analyzed their influence on chromatin stability and revealed that LCS-1269 displaces histone H1. Our analysis of chromatin remodeling also included a wide set of epigenetic experiments in which LCS-1269 demonstrated complex epigenetic activity. Finally, we revealed that the antitumor effect of the compounds is based not only on binding to DNA and chromatin remodeling but also on alternative mechanisms. Both compounds induce expression changes in genes involved in neoplastic transformation and target genes of the signaling pathways in cancer cells. Despite of being structurally similar, each compound has unique biological activities. The effects of LCS-1208 are associated with intercalation. The mechanisms of LCS-1269 include influence on higher levels such as chromatin remodeling and epigenetic effects.

scholarly journals Design, synthesis, anticancer activity and docking studies of theophylline containing 1,2,3-triazoles with variant amide derivatives

MedChemComm ◽  
2017 ◽  
Vol 8 (1) ◽  
pp. 176-183 ◽  
Author(s):  
Radhakrishnam Raju Ruddarraju ◽  
Adharvana Chari Murugulla ◽  
Ravindar Kotla ◽  
Muni Chandra Babu Tirumalasetty ◽  
Rajendra Wudayagiri ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Docking Studies ◽  
Design Synthesis ◽  
Amide Derivatives

A new series of theophylline analogues containing 1,2,3-triazoles with different amide groups (22–41) has been designed and synthesized, and their biological activities have been evaluated as potential anticancer agents.

Sign in / Sign up

Export Citation Format

Share Document