RESUMO
Monocarbonyl analogs of curcumin (MACs) represent structurally modified versions of curcumin. The existing literature indicates that MACs exhibit enhanced anticancer properties compared with curcumin. Numerous research articles in recent years have emphasized the significance of MACs as effective anticancer agents. This review focuses on the latest advances in the anticancer potential of MACs, from 2014 to 2024, including discussions on their mechanism of action, structure-activity relationship (SAR), and in silico molecular docking studies.
RESUMO
Curcumin is an important phytochemical, found in the Asian countries, especially in the Indian subcontinent. The use of this "privileged natural product" in the diversity-oriented synthesis of curcumin-based heterocycles via multicomponent reactions (MCRs) is the subject of interest for many medicinal chemists across the globe. This review particularly focuses on the reactions involving curcuminoids as one of the reactants in the MCRs of curcuminoid to synthesize curcumin-based heterocycles. Also, the various pharmacological activities of curcumin-based heterocycles generated via the MCR approach are discussed. The research work published in the last 10 years is in the focus of this review article.
Assuntos
Produtos Biológicos , Curcumina , Curcumina/farmacologia , Relação Estrutura-Atividade , Diarileptanoides , Produtos Biológicos/farmacologiaRESUMO
In search for new fungicidal and free radical scavenging agents, we synthesized a focused library of 2-chloroquinoline based monocarbonyl analogs of curcumin (MACs). The synthesized MACs were evaluated for inâ vitro antifungal and antioxidant activity. The antifungal activity was evaluated against five different fungal strains such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger, and Cryptococcus neoformans, respectively. Most of the synthesized MACs displayed promising antifungal activity compared to the standard drug Miconazole. Furthermore, molecular docking study on a crucial fungal enzyme sterol 14α-demethylase (CYP51) could provide insight into the plausible mechanism of antifungal activity. MACs were also screened for inâ vitro radical scavenging activity using butylated hydroxytoluene (BHT) as a standard. Almost all MACs exhibited better antioxidant activity compared to BHT.
Assuntos
Antifúngicos/síntese química , Antioxidantes/química , Curcumina/análogos & derivados , Proteínas Fúngicas/metabolismo , Simulação de Acoplamento Molecular , Quinolinas/química , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Sítios de Ligação , Candida albicans/efeitos dos fármacos , Domínio Catalítico , Cryptococcus neoformans/efeitos dos fármacos , Curcumina/metabolismo , Curcumina/farmacologia , Proteínas Fúngicas/química , Testes de Sensibilidade Microbiana , Esterol 14-Desmetilase/química , Esterol 14-Desmetilase/metabolismoRESUMO
A series of new 1,2,3-triazole-tethered coumarin conjugates linked by N-phenylacetamide was efficiently synthesized via the click chemistry approach in excellent yields. The synthesized conjugates were evaluated for their in vitro antifungal and antioxidant activities. Antifungal activity determination was carried out against fungal strains such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. Compounds 7b, 7d, 7e, 8b and 8e displayed higher potency than the standard drug miconazole, with lower minimum inhibitory concentration values. Also, compound 7a exhibited potential radical scavenging activity as compared with the standard antioxidant butylated hydroxytoluene. In addition, a molecular docking study of the newly synthesized compounds was carried out, and the results showed a good binding mode at the active site of the fungal (C. albicans) P450 cytochrome lanosterol 14α-demethylase enzyme. Furthermore, the synthesized compounds were also tested for ADME properties, and they demonstrated potential as good candidates for oral drugs.
Assuntos
Antifúngicos/farmacologia , Antioxidantes/farmacologia , Cumarínicos/farmacologia , Fungos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Triazóis/farmacologia , Administração Oral , Antifúngicos/administração & dosagem , Antifúngicos/síntese química , Antioxidantes/administração & dosagem , Antioxidantes/síntese química , Disponibilidade Biológica , Química Click , Cumarínicos/administração & dosagem , Cumarínicos/síntese química , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/administração & dosagem , Triazóis/síntese químicaRESUMO
A search for potent antiproliferative agents has prompted to design and synthesize aryloxy bridged and amide linked dimeric 1,2,3-triazoles (7a-j) by using 1,3-dipolar cycloaddition reaction between 2-azido-N-phenylacetamides (4a-e) and bis(prop-2-yn-1-yloxy)benzenes (6a-b) via copper (I)-catalyzed click chemistry approach with good to excellent yields. All the newly synthesized compounds have been screened for their in vitro antiproliferative activities against two human cancer cell lines. The compounds 7d, 7e, 7h, 7i and 7j have revealed promising antiproliferative activity against human breast cancer cell line (MCF-7), whereas, the compounds 7a, 7b, 7c, 7i and 7j were observed as potent antiproliferative agents against human lung cancer cell line (A-549). The active compounds against MCF-7 have been also analysed for their mechanism of action by the enzymatic study, which shows that the compounds 7d, 7h and 7j were acts as active EGFR tyrosine kinase phosphorylation inhibitors. In support to this biological study, the molecular docking as well as in silico ADME properties of all the newly synthesized hybrids were predicted.
Assuntos
Amidas/química , Antineoplásicos/farmacologia , Proliferação de Células , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Triazóis/química , Antineoplásicos/química , Química Click , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Neoplasias/patologia , Fosforilação , Inibidores de Proteínas Quinases/química , Relação Estrutura-AtividadeRESUMO
A series of quinoline incorporated monocarbonyl curcumin analogues was efficiently synthesized using [HDBU][HSO4] as catalyst via Knoevenagel type condensation and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG in dormant state. The analogues 3e, 3h, 4a and 4e exhibited very good antitubercular activity. The antiproliferative activity of the analogues against MCF-7, A549 and HCT-116 cell lines was evaluated using modified MTT assay and these compounds were found to be non-cytotoxic. Molecular docking study has been carried out against M. tuberculosis pantothenate synthetase (MTB PS) enzyme in an effort to enhance the understanding of their action as antitubercular agents. The potency, low cytotoxicity and selectivity of these analogues support them as valid leads for further optimization.
Assuntos
Antituberculosos/química , Antituberculosos/farmacologia , Curcumina/análogos & derivados , Curcumina/farmacologia , Quinolinas/química , Linhagem Celular Tumoral , Curcumina/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacosRESUMO
We have developed, highly efficient, one-pot, solvent-free, [Et3NH][HSO4] catalyzed multicomponent reaction protocol for the synthesis of 1,3-thiazolidin-4-ones in excellent yields. For the first time, the 1,3-thiazolidin-4-ones were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis dormant MTB H37Ra and Mycobacterium bovis BCG strains. Among the synthesized basic 1,3-thiazolidin-4-ones, particularly the compounds 4c, 4d, 4e, 4f, 4h, 4i and 4j displays promising antitubercular activity along with no significant cytotoxicity against the cell lines MCF-7, A549 and HCT-116.
Assuntos
Antituberculosos/química , Antituberculosos/farmacologia , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Tiazolidinas/química , Tiazolidinas/farmacologia , Tuberculose/tratamento farmacológico , Animais , Antituberculosos/síntese química , Linhagem Celular , Técnicas de Química Combinatória/economia , Técnicas de Química Combinatória/métodos , Química Verde/economia , Química Verde/métodos , Humanos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Tiazolidinas/síntese química , Tuberculose/veterináriaRESUMO
In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and M. bovis BCG, a small focused library of benzothiazinone based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be promising inhibitors of MTB and M. bovis BCG characterized by lower MIC values (27.34-29.37µg/mL). Among all the synthesized compounds, 6c and 6e is the most active compound against MTB and M. bovis BCG. The compounds were further tested for anti-proliferative activity against HeLa, A549 and A431 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activity with IC50 range=14.14-47.11µg/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target MTB DprE1, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole incorporated benzothiazinone may possess the ideal structural requirements for further development of novel therapeutic agents.
Assuntos
Antituberculosos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Tiazinas/farmacologia , Triazóis/farmacologia , Oxirredutases do Álcool/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antituberculosos/síntese química , Antituberculosos/química , Proteínas de Bactérias/química , Linhagem Celular Tumoral , Química Click , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/química , Humanos , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Tiazinas/síntese química , Tiazinas/química , Triazóis/síntese química , Triazóis/químicaRESUMO
In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and Mycobacterium bovis BCG, a small focused library of rhodanine incorporated tetrazoloquinoline has been efficiently synthesized by using [HDBU][HSO4] acidic ionic liquid. The compound 3c found to be promising inhibitor of MTB H37Ra and M. bovis BCG characterized by lower MIC values 4.5 and 2.0 µg/mL, respectively. The active compounds were further tested for cytotoxicity against HeLa, THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Again, the synthesized compounds were found to have potential antifungal activity. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target Zmp1 enzyme of MTB H37Ra, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of in vitro and in silico study suggest that these compounds possess ideal structural requirement for the further development of novel therapeutic agents.
Assuntos
Quinolinas/síntese química , Quinolinas/farmacologia , Rodanina/química , Quinolinas/químicaRESUMO
An efficient and greener protocol for the synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one using tetradecyltrimethylammonium bromide (TTAB) at room temperature in water is described.
RESUMO
The present work describes design of a small library of new 1,2,3-triazole-appended bis-pyrazoles by using a molecular hybridization approach, and the synthesized hybrids were evaluated for their antifungal activity against different fungal strains, namely, Candida albicans, Cryptococcus neoformans, Candida glabrata, Candida tropicalis, Aspergillus niger, and Aspergillus fumigatus. All the compounds exhibited broad-spectrum activity against the tested fungal strains with excellent minimum inhibitory concentration values. The molecular docking study against sterol 14α-demethylase (CYP51) could provide valuable insights into the binding modes and affinity of these compounds. Furthermore, these compounds were also evaluated for their antioxidant activity, which also resulted in promising data.
RESUMO
A synthesis of ±-cherylline dimethyl ether is reported. The key steps involved are Michael-type addition, radical azidonation of an aldehyde, Curtius rearrangement, and reduction of an isocyanate intermediate followed by Pictet-Spengler cyclization.
RESUMO
BACKGROUND & OBJECTIVE: Novel 1,2,3-triazole based benzylidenehydrazide derivatives were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra, M. bovis BCG and cytotoxic activity. Most of the derivatives exhibited promising in vitro potency against MTB characterized by lower MIC values. METHODS: Among all the synthesized derivatives, compound 6a and 6j were the most active against active and dormant MTB H37Ra, respectively. Compound 6d was significantly active against dormant and active M. bovis BCG. RESULTS: The structure activity relationship has been explored on the basis of anti-tubercular activity data. The active compounds were also tested against THP-1, A549 and Panc-1 cell lines and showed no significant cytotoxicity. Further, the synthesized compounds were found to have potential antioxidant with IC50 range = 11.19-56.64 µg/mL. The molecular docking study of synthesized compounds was performed against DprE1 enzyme of MTB to understand the binding interactions. CONCLUSION: Furthermore, synthesized compounds were also analysed for ADME properties and the potency of compounds indicated that, this series can be considered as a starting point for the developement of novel and more potent anti-tubercular agents in future.
Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Antituberculosos/farmacologia , Compostos de Benzilideno/farmacologia , Simulação de Acoplamento Molecular , Mycobacterium/efeitos dos fármacos , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Antituberculosos/síntese química , Antituberculosos/química , Compostos de Benzilideno/síntese química , Compostos de Benzilideno/química , Compostos de Bifenilo/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Picratos/antagonistas & inibidores , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/químicaRESUMO
A facile, highly efficient, and greener method for the synthesis of new 1,4-disubstituted-1,2,3-triazoles was conducted using [Et3NH][OAc] as a medium by the implementation of ultrasound irradiation via click chemistry, affording excellent yields. The present synthetic method exhibited numerous advantages such as mild reaction conditions, excellent product yields, minimal chemical waste, operational simplicity, shorter reaction time, and a wide range of substrate scope. The synthesized compounds were further evaluated for in vitro antifungal activity against five fungal strains, and some of the compounds displayed equivalent or greater potency than the standard drug. A molecular docking study against the modelled three-dimensional structure of cytochrome P450 lanosterol 14α-demethylase was also performed to understand the binding affinity and binding interactions of the enzyme. Furthermore, the synthesized compounds were evaluated for DPPH radical scavenging activity and antitubercular activity against Mycobacterium tuberculosis H37Rv strain.
RESUMO
We describe the synthesis of novel triazole-incorporated diindolylmethanes (DIMs) using a molecular hybridization approach. The in vitro antitubercular activity of the DIMs against Mycobacterium tuberculosis H37Ra (ATCC 25177) was tested in the active and dormant state. Among all the synthesized conjugates, the compounds 6b, 6f, 6l, 6n, 6q, 6r, and 6s displayed good antitubercular activity against both the active and dormant Mtb H37Ra strain. The compound 6l exhibited good antitubercular activity against dormant Mtb H37Ra with an IC50 value of 1 µg mL-1 and IC90 (MIC) value of 3 µg mL-1. The compounds 6b, 6l, and 6r displayed good antitubercular activity against active Mtb H37Ra with IC50 values of 2.19, 1.52, and 0.22 µg mL-1, respectively. The compounds 6b, 6h, 6l, and 6s displayed more than 70% inhibition against the Gram-positive Bacillus subtilus strain at 3 µg mL-1. The molecular docking study showed the binding modes of the titled compounds in the active site of the DprE1 enzyme and assisted with elucidating a structural basis for the inhibition of Mycobacteria.
RESUMO
OBJECTIVE: We have synthesized new quinolidinyl-thiazolidinones via Knoevenagel condensation- alkylation reaction, catalyzed by [Et3NH][HSO4]. The present approach offers several advantages such as higher yields, eco-friendly reaction condition and economic availability of the catalyst. METHOD: The newly synthesized compounds were evaluated for their in vitro antifungal activity against six fungal strains. Some of the synthesized conjugates displayed good to moderate antifungal activity. CONCLUSION: Again, the molecular docking study performed against the fungal sterol 14α-demethylase (CYP51) showed an excellent binding affinity towards the enzyme which could rationalize the promising antifungal activity portrayed by these derivatives and provides a platform for structure based drug design.
Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Simulação de Acoplamento Molecular , Tiazolidinas/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Tiazolidinas/síntese químicaRESUMO
A series of rhodanine incorporated quinoline derivatives were efficiently synthesized using reusable DBU acetate as ionic liquid and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) both in active and dormant state. Compounds 3e, 3f, 3g, 3h and 3i exhibited very good antitubercular activity. The active compounds were studied for cytotoxicity against HUVEC, THP-1, macrophages, A549, PANC-1 and HeLa cell lines using modified MTT assay and were found to be noncytotoxic. Inactivity of all these compounds against Gram positive and Gram negative bacteria indicates their specificity towards the MTB. Further, the synthesized compounds have been screened for their in vitro antifungal activity. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of Zmp1 enzyme, which in turn helped to establish a structural basis of inhibition of mycobacteria. The results of present study clearly indicate the identification of some novel, selective and specific inhibitors against MTB that can be explored further for potential antitubercular drug.
Assuntos
Antituberculosos/química , Antituberculosos/farmacologia , Mycobacterium bovis/efeitos dos fármacos , Quinolinas/química , Quinolinas/farmacologia , Rodanina/análogos & derivados , Rodanina/química , Rodanina/farmacologia , Animais , Antituberculosos/síntese química , Proteínas de Bactérias/metabolismo , Linhagem Celular , Humanos , Metaloproteases/metabolismo , Simulação de Acoplamento Molecular , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium/veterinária , Mycobacterium bovis/metabolismo , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/metabolismo , Quinolinas/síntese química , Rodanina/síntese químicaRESUMO
Homologation of 16-dehydropregnenolone acetate leads to excellent stereocontrolled synthesis of unnatural C (20R) aldehydes and through compound .
RESUMO
Stereoselective synthesis of novel steroidal C-20 tertiary alcohols with thiazole and pyridine side chain using Grignard reaction of steroidal ketones and thiazole/pyridine magnesium bromide have been realized. These molecules were evaluated in vitro for their antifungal and antibacterial activities. Most of the compounds exhibited significant antifungal and antibacterial activity against all the tested strains.