Despite a significant work that has been done on thiophene, continuous efforts are still being made by the researchers to identify novel heterocyclic compounds with potential bioactivities. Thiophene ...nucleus has been extensively utilized by the researchers across the globe for the development of diverse bioactive heterocycles for hitting a wide range of biological targets. This review throws light on synthetic approaches that have been used for the synthesis of potential thiophene derivatives followed by the depth analysis of them with respect to their pharmacological significance. This review can help the medicinal chemists and researchers to develop novel leads having thiophene nucleus with high efficacy and reduced side effects.
Keeping in view various pharmacological attributes of indole and coumarin derivatives, a new series of indolindione–coumarin molecular hybrids was rationally designed and synthesized. All synthesized ...hybrid molecules were evaluated for their antimicrobial potential against Gram-negative bacterial strains (Escherichia coli and Salmonella enterica), Gram-positive bacterial strains (Staphylococcus aureus and Mycobacterium smegmatis), and four fungal strains (Candida albicans, Alternaria mali, Penicillium sp., and Fusarium oxysporum) by using the agar gel diffusion method. Among all synthetics, compounds K-1 and K-2 were found to be the best antimicrobial agents with the minimum inhibitory concentration values of 30 and 312 μg/mL, against Penicillium sp. and S. aureus, respectively. The biological data revealed some interesting facts about the structure–activity relationship which state that the electronic environment on the indolinedione moiety and carbon chain length between indolinedione and triazole moieties considerably affect the antimicrobial potential of the synthesized hybrids. Various types of binding interactions of K-2 within the active site of S. aureus dihydrofolate reductase were also streamlined by molecular modeling studies, which revealed the possible mechanism for potent antibacterial activity of the compound.
A library of indolinedione–coumarin hybrid molecules was rationally designed and synthesized against hyperuricemia. All of the synthesized hybrid molecules were tested to check their inhibitory ...activity against xanthine oxidase enzyme by using a spectrophotometric assay. The results revealed that the compound showed IC
50
values within the range of 6.5–24.5 µM amongst which compound
K-7
was found to be endowed with the most potent IC
50
value against xanthine oxidase enzyme. Kinetic studies were also performed to check the mode of inhibition of most potent compound
K-7
, which revealed its mixed-type inhibition behavior. Structure-activity relationships revealed that electron-donating groups and small alkyl chains between the two active scaffolds might be beneficial in inhibiting xanthine oxidase enzyme. It was also shown that various electrostatic interactions stabilized the compound
K-7
within the active site of xanthine oxidase enzyme, which confirmed that it can completely block its catalytic active site. Thus,
K-7
is regarded as a potent xanthine oxidase inhibitor and can be served as a promising molecular architectural unit for anti-hyperuricemic drug design.
Breast cancer is the most prominent, frequently diagnosed and leading cause of death among women. Estrogen is an agonist of estrogen receptor alpha (ER-α), expressed in mammary glands and is ...responsible for initiating many signalling pathways that lead to differentiation and development of breast tissue. Any mutations in these signalling pathways result in irregular growth of mammary tissue, leading to the development of tumour or cancer. All these observations attract the attention of researchers to antagonize ER-α receptor either by developing selective estrogen receptor modulators or by selective estrogen receptor degraders. Therefore, this article provides a brief overview of various factors that are responsible for provoking breast cancer in women and design strategies recently used by the various research groups across the world for antagonizing or demodulating ER-α.
Graphic abstract
A series of 22 compounds of thiazole-5-carboxylic acid derivatives was rationally designed and synthesized. All the compounds were characterized by using
1
H and
13
C NMR and tested against xanthine ...oxidase enzyme by spectrophotometric assay. Majority of the compounds were found active against the enzyme amongst which
GK-20
with an IC
50
value of 0.45 µM was found to be most potent. Structure-activity relationship obtained from the biological results revealed that the di-substituted compounds as Ring B were more potent than that of mono-substituted derivatives.
Para
-substitution on Ring B is crucial for the xanthine oxidase inhibitory potential. Enzyme kinetic studies further revealed their mixed type inhibition behavior. Moreover, the binding pattern of the most potent compound
GK-20
within the febuxostat binding site of the enzyme was further analyzed by using docking studies which revealed that it sufficiently block the catalytic active site, which prevents the substrate to bind.
Nanoformulation-based combinational drug delivery systems are well known to overcome drug resistance in cancer management. Among them, nanoemulsions are well-known and thermodynamically stable drug ...delivery systems suitable for carrying hydrophobic drugs and phytoconstituents to tackle drug-resistant cancers. In the present study, we have investigated the effect of paclitaxel in combination with erucin (natural isothiocyanate isolated from the seeds of
Eruca sativa
) loaded in the frankincense oil-based nanoemulsion formulation. The choice of frankincense oil for the current study was based on reported research investigations stating its magnificient therapeutic potential against breast cancer. Optimized nanoemulsion of paclitaxel (PTX) and erucin (ER) combination (EPNE) provided sustained release and exhibited enhanced cytotoxicity towards human epithelial breast cancer cells (T-47D) as compared to individual ER and PTX. EPNE was further assessed for its antitumor activity in the 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer mice model. EPNE significantly decreased the levels of hepatic and renal parameters along with oxidative stress in breast cancer mice. Furthermore, EPNE also showed decreased levels of inflammatory cytokines TNF-α, IL-6. Histopathological examinations revealed restoration of the tumorous breast to normal tissues in EPNE-treated breast cancer mice. Therefore, EPNE can act as a viable lead and therapeutic option for drug-resistant breast cancer.
Grewia asiatica Linn. is a well-known plant for its nutritional and therapeutic attributes. It has been mentioned in ancient Indian literature as Rasayana due to its stimulant and tonic effects. ...Thus, present investigation was carried out to evaluate the antiepileptic and anxiolytic action of G. asiatica Linn. leaves using animal models. Methanol extract at dose levels of 100 and 200 mg/kg was capable of providing protection against both pentylenetetrazole and maximal electroshock induced seizures in mice. Extract also showed significant anxiolytic activity in elevated plus maze, light/dark box and mirror chamber mice models at same dose levels. Results of this study indicated that the methanol extract of leaves of G. asiatica plant possess significant antiepileptic and anxiolytic effect.
Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in ...clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure–activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents.
Non melanoma skin cancers are common neoplasms worldwide. In India, squamous cell carcinoma (SCC), is the most prevalent skin disorder and its incidence rises quickly with cumulative exposure to sun. ...Numerous techniques are available for SCC but reversion and metastasis are common concern that needs effective and safe strategies for its control. With this in view, the study was planned to investigate the activity of Bakuchiol (Bak), traditionally used in various countries for curing skin ailments but its mechanism of action is unexplored. In our study, we explored anti-proliferative, pro-apoptotic and anti-inflammatory potential of Bak toward human squamous carcinoma (A431) cell line.
The pure compound Bak was isolated from the plant Psoralea corylifolia and characterized using NMR, HRMS and FTIR. To explore their bioefficacy, different in vitro assays were performed against A431 cell line. To have molecular insights, RT-qPCR investigation was done to analyzed the expression level of inflammatory markers (TLR 9, IFN β, IL 23, JAK 3 and STAT 3).
The results showed the growth inhibitory effect on A431 cells after Bak treatment in dose-dependent way. To understand mode of cell death, cells were initially analyzed under phase-contrast, fluorescence and scanning electron microscope that showed characteristics of apoptosis. Furthermore, cell cycle studies with a flow cytometer were carried out which showed increased level of ROS, reduced MMP and cells arrested at G0/G1 phase in Bak treated cells further strengthening the induction of apoptosis. Moreover, RT-qPCR analysis indicated the downregulation of inflammatory markers in Bak-treated A431 cells that further confirmed its therapeutic role. The molecular docking study also confirmed that Bak has perfect scaffold that can complete the pharmacophoric need for JAK3 kinase inhibition.
A critical analysis of results points towards the role of Bak in ameliorating inflammatory markers along with apoptosis induction in A431 cells by regulating the expression level of variable markers.
Lack of treatment of novel Coronavirus disease led to the search of specific antivirals that are capable to inhibit the replication of the virus. The plant kingdom has demonstrated to be an important ...source of new molecules with antiviral potential.
The present study aims to utilize various computational tools to identify the most eligible drug candidate that have capabilities to halt the replication of SARS-COV-2 virus by inhibiting Main protease (Mpro) enzyme
We have selected plants whose extracts have inhibitory potential against previously discovered coronaviruses. Their phytoconstituents were surveyed and a library of 100 molecules was prepared. Then, computational tools such as molecular docking, ADMET and molecular dynamic simulations were utilized to screen the compounds and evaluate them against Mpro enzyme.
All the phytoconstituents showed good binding affinities towards Mpro enzyme. Among them laurolitsine possesses the highest binding affinity i.e. -294.1533 kcal/mol. On ADMET analysis of best three ligands were simulated for 1.2 ns, then the stable ligand among them was further simulated for 20 ns. Results revealed that no conformational changes were observed in the laurolitsine w.r.t. protein residues and low RMSD value suggested that the Laurolitsine-protein complex was stable for 20 ns.
Laurolitsine, an active constituent of roots of Lindera aggregata, was found to be having good ADMET profile and have capabilities to halt the activity of the enzyme. Therefore, this makes laurolitsine a good drug candidate for the treatment of COVID-19.
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