Molecular docking, DFT and antiproliferative properties of 4-(3,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine as potent anticancer agent with CDK2 and PIM1 inhibition potency.

Due to the limited effeteness and safety concerns associated with current cancer treatments, there is a pressing need to develop novel therapeutic agents. 4-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine (3) was synthesized and Initially screened on 59 cancer cell lines showed promising anticancer activity, so, it was chosen for a 5-dose experiment by the NCI/USA. The GI values ranged from 1.

Novel imidazo[2,1-b]thiazoles and imidazo[1,2-a]pyridines tethered with indolinone motif as VEGFR-2 inhibitors and apoptotic inducers: Design, synthesis and biological evaluations.

The current study investigates the anticancer and VEGFR-2 inhibitory activities of 16 novel indolinone-grafted imidazo[2,1-b]thiazole and imidazo[1,2-a]pyridine derivatives (6a-h and 10a-h). The structures of these target compounds were confirmed using elemental and spectral analyses. All compounds were evaluated for their VEGFR-2 inhibitory activity in vitro, with eight compounds demonstrating promising results, exhibiting IC values in the sub-micromolar range (0.

New Thiazolyl-Pyrazoline Derivatives as Potential Dual EGFR/HER2 Inhibitors: Design, Synthesis, Anticancer Activity Evaluation and In Silico Study.

new series of thiazolyl-pyrazoline derivatives (-, -, , -, , , and , ) have been designed and synthesized through the combination of thiazole and pyrazoline moieties, starting from the key building blocks pyrazoline carbothioamides (-). These eighteen derivatives have been designed as anticipated EGFR/HER2 dual inhibitors. The efficacy of the developed compounds in inhibiting cell proliferation was assessed using the breast cancer MCF-7 cell line.

Synthesis and In Vitro Anticancer Activity of Novel 4-Aryl-3-(4-methoxyphenyl)-1-phenyl-1-pyrazolo[3,4-]pyridines Arrest Cell Cycle and Induce Cell Apoptosis by Inhibiting CDK2 and/or CDK9.

Two series of pyrazolo[3,4-]pyridine derivatives, - and -, are synthesized and evaluated for their anti-cancer potency towards Hela, MCF7, and HCT-116 cancer cell lines. Compound showed the highest anticancer activity with IC = 2.59 µM against Hela when compared with doxorubicin (IC = 2.

Discovery of pyrimidine-tethered benzothiazole derivatives as novel anti-tubercular agents towards multi- and extensively drug resistant .

In this study, new benzothiazole-pyrimidine hybrids (-, , -, and -) were designed and synthesised. Two different functionalities on the pyrimidine moiety of lead compound were subjected to a variety of chemical changes with the goal of creating various functionalities and cyclisation to further elucidate the target structures. The potency of the new molecules was tested against different tuberculosis (TB) strains.

Investigating the promising SARS-CoV-2 main protease inhibitory activity of secoiridoids isolated from ; and assessments with structure-activity relationship.

The proteolytic enzyme 3 C-like protease (3Clpro or M) is considered the most important target for SARS-CoV-2 which could be attributed to its crucial role in viral maturation and/or replication. Besides, natural phytoconstituents from plant origin are always promising lead compounds in the drug discovery area. Herein, the previously isolated and identified seven compounds from () were examined and against the SARS-CoV-2 M.

Design and synthesis of 6-arylpyridine-tethered sulfonamides as novel selective inhibitors of carbonic anhydrase IX with promising antitumor features toward the human colorectal cancer.

Hypoxia, a characteristic feature of solid tumors, develops as a result of excessive cell proliferation and rapid tumor growth exceeding the oxygen supply, and can result in angiogenesis activation, increased invasiveness, aggressiveness, and metastasis, leading to improved tumor survival and suppression of anticancer drug therapeutic impact. SLC-0111, a ureido benzenesulfonamide, is a selective human carbonic anhydrase (hCA) IX inhibitor in clinical trials for the treatment of hypoxic malignancies. Herein, we describe the design and synthesis of novel 6-arylpyridines 8a-l and 9a-d as structural analogues of SLC-0111, in the aim of exploring new selective inhibitors for the cancer-associated hCA IX isoform.

Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of -(5-nitrothiazol-2-yl)-carboxamido candidates: and studies.

In this article, emulsomes (EMLs) were fabricated to encapsulate the -(5-nitrothiazol-2-yl)-carboxamido derivatives (-) in an attempt to improve their biological availability and antiviral activity. Next, both cytotoxicity and anti-SARS-CoV-2 activities of the examined compounds loaded EMLs (-) were assessed in Vero E6 cells via MTT assay to calculate the CC and inhibitory concentration 50 (IC) values. The most potent -loaded EMLs () elicited a selectivity index of 18 with an IC value of 0.

Metabolomic profile, anti-trypanosomal potential and molecular docking studies of .

Trypanosomiasis is a protozoan disease transmitted via  This study aimed to examine the metabolic profile and anti-trypanosomal effect of methanol extract of leaves. The liquid chromatography-high resolution electrospray ionisation mass spectrometry (LC-HRESIMS) revealed the identification of fifteen compounds of iridoid, flavonoid, lignan, phenolic acid, and alkaloid classes. The extract displayed a promising inhibitory activity against TC 221 with MIC value of 1.

Identification of new 4-(6-oxopyridazin-1-yl)benzenesulfonamides as multi-target anti-inflammatory agents targeting carbonic anhydrase, COX-2 and 5-LOX enzymes: synthesis, biological evaluations and modelling insights.

Multiple inhibitions of CA, COX-2 and 5-LOX enzymes has been recognised as a useful strategy for the development of anti-inflammatory drugs that can avoid the disadvantages of using NSAIDs alone. Here, we report new pyridazine-based sulphonamides ( and ) as potential multi-target anti-inflammatory candidates. First, the furanone heterocycle in the dual CA/COX-2 inhibitor Polmacoxib was replaced with the pyridazinone one.

Synergistic Effect of and Flavonoid-Rich Fractions on Wound Healing: and Molecular Docking Studies.

and (Fabaceae) are well-known medicinal plants with valuable secondary metabolites and pharmacological properties. The flavonoid-rich fractions of roots and leaves were prepared using Diaion column chromatography, and the confirmation of flavonoid richness was confirmed using UPLC-ESI-MS profiling and total phenolics and flavonoids assays. UPLC-ESI-MS profiling of the flavonoid-rich fraction of roots and leaves resulted in the tentative identification of 32 and 23 compounds, respectively.

GC/MS Profiling of the Essential Oil and Lipophilic Extract of Boiss. and Evaluation of Their Cytotoxic and Antioxidant Activities.

The genus (Brassicaceae) comprises about eight species that were used in traditional medicine. is used to alleviate certain disorders such as syphilis and exhibits analgesic, anti-inflammatory, antipyretic, antioxidant, and antigenotoxic properties. Throughout this study, we aimed to figure out the chemical composition of lipophilic extract and essential oil obtained from aerial parts using GC/MS analysis, as well as their cytotoxic and antioxidant activities correlated with the major detected compounds' molecular docking.

Development of potent nanosized carbonic anhydrase inhibitor for targeted therapy of hypoxic solid tumors.

Overexpression of two carbonic anhydrase (CA) isoforms, CA IX and XII, in several hypoxic solid tumors provides an extracellular hypoxic microenvironment, interferes with extra- and intracellular pH regulation, thus favoring hypoxic tumor cell survival, proliferation and metastasis. In the current study, a selective inhibitor for human CA isoforms IX and XII (isatin-bearing sulfonamide, WEG-104), was incorporated into nanosized spherical niosomes at high encapsulation efficiency to allow for an enhanced and sustained antitumor activity. In vivo, administration of WEG-104 that is either free (10 mg/kg) or loaded into niosomes (5 mg/kg) into a mice model of Ehrlich ascites solid tumor resulted in comparable efficacy in terms of reduction of tumor weight and volume.

Chemical Constituents, Antioxidant, and Enzyme Inhibitory Activities Supported by In-Silico Study of -Hexane Extract and Essential Oil of Guava Leaves.

Psidium guajava (Guava tree) is one of the most widely known species in the family Myrtaceae. The Guava tree has been reported for its potential antioxidant, anti-inflammatory, antimicrobial, and cytotoxic activities. In the current study, the chemical compositions of the n-hexane extract and the essential oil of P.

The Antioxidant and Enzyme Inhibitory Potential of -Hexane-Extracted Oils Obtained from Three Egyptian Cultivars of the Golden Dewdrop Linn. Supported by Their GC-MS Metabolome Analysis and Docking Studies.

Linn. has a longstanding history for use in folk remedy for several disorders. Its hydroalcoholic extract has been investigated intensely in the treatment of many ailments, but to date very few data are presented to explain the pharmacological use of its oil.

Enaminone-based carboxylic acids as novel non-classical carbonic anhydrases inhibitors: design, synthesis and biological assessment.

In searching for new molecular drug targets, Carbonic Anhydrases (CAs) have emerged as valuable targets in diverse diseases. CAs play critical functions in maintaining pH and CO homeostasis, metabolic pathways, and much more. So, it is becoming attractive for medicinal chemists to design novel inhibitors for this class of enzymes with improved potency and selectivity towards the different isoforms.

In Silico Docking, Resistance Modulation and Biofilm Gene Expression in Multidrug-Resistant via Cinnamic and Gallic Acids.

Despite the mounting global burden of antimicrobial resistance (AMR), the generation of new classes of effective antimicrobials still lags far behind. The interplay between multidrug resistance and biofilm formation in Acinetobacter baumannii has drastically narrowed the available therapeutic choices. The use of natural compounds holds promise as an alternate option for restoring the activity of existing antibiotics and attenuating virulence traits through reduced biofilm formation.

GC/MS analysis and potential synergistic effect of mandarin and marjoram oils on .

can cause chronic gastritis, peptic ulcer, and gastric carcinoma. This study compares chemical composition and activity of mandarin leaves and marjoram herb essential oils, and their combined oil. GC/MS analysis of mandarin oil revealed six compounds (100% identified), mainly methyl--methyl anthranilate (89.

Phytonutrients, Colorant Pigments, Phytochemicals, and Antioxidant Potential of Orphan Leafy Species.

The underutilized leafy vegetables are a unique basis of pigments such as β-cyanins, β-xanthins, and betalains with radical scavenging capacity (RSC). They have abundant phytonutrients and antioxidant components, such as pigments, vitamins, phenolics, and flavonoids. Eight selected genotypes (four genotypes from each species) of underutilized leafy vegetables were evaluated for phytonutrients, pigments, vitamins, phenolics, flavonoids, and antioxidants in a randomized complete block design under ambient field conditions with three replicates.

Development of 4-((3-oxo-3-phenylpropyl)amino)benzenesulfonamide derivatives utilizing tail/dual-tail approaches as novel carbonic anhydrase inhibitors.

In the current work, we adopted the tail/dual tail approaches to design and synthesize the benzenesulfonamide derivatives 6a-b, 8, 10a-b, 12a-b, 14, and 16 as new SLC-0111 analogs endowed with carbonic anhydrase (CA) inhibitory activity. All the prepared benzenesulfonamide derivatives were tested for their inhibitory action towards hCA isoforms; hCA I, II, IX, and XII. The results revealed their ability to affect the examined isoforms in variable degrees with K ranges: 49.

identification of potential SARS COV-2 2'--methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations.

In the present era, there are many efforts trying to face the emerging and successive waves of the COVID-19 pandemic. This has led to considering new and unusual targets for SARS CoV-2. 2'--Methyltransferase (nsp16) is a key and attractive target in the SARS CoV-2 life cycle since it is responsible for the viral RNA protection a cap formation process.

Novel 3-(6-methylpyridin-2-yl)coumarin-based chalcones as selective inhibitors of cancer-related carbonic anhydrases IX and XII endowed with anti-proliferative activity.

Carbonic anhydrases (CAs) are one of the promising targets for the development of anticancer agents. CA isoforms are implicated in various physiological processes and are expressed in both normal and cancerous cells. Thus, non-isoform selective inhibitors are associated with several side effects.

GC/MS Profiling, Anti-Collagenase, Anti-Elastase, Anti-Tyrosinase and Anti-Hyaluronidase Activities of a Leaves Extract.

Today, skin care products and cosmetic preparations containing natural ingredients are widely preferred by consumers. Therefore, many cosmetic brands are encouraged to offer more natural products to the market, such as plant extracts that can be used for their antiaging, antiwrinkle, and depigmentation properties and other cosmetic purposes. In the current study, the volatile constituents of the hexane-soluble fraction of a (family Proteaceae) leaf methanol extract (SSHF) were analyzed using GC/MS analysis.

Fenticonazole nitrate loaded trans-novasomes for effective management of tinea corporis: design characterization, study, and exploratory clinical appraisal.

The current investigation aimed for loading fenticonazole nitrate (FTN), an antifungal agent with low aqueous solubility, into trans-novasomes (TNs) for management of tinea corporis topically. TNs contain Brij as an edge activator besides the components of novasomes (cholesterol, Span 60, and oleic acid) owing to augment the topical delivery of FTN. TNs were fabricated applying ethanol injection method based on D-optimal experiment.