Flavone-C-glycosides from L. as possible inhibitors of phosphodiesterase-5 (PDE5): , molecular docking and molecular dynamics studies.

Phosphodiesterase-5 (PDE5) is a homodimeric enzyme that specifically targets cyclic guanosine monophosphate (cGMP), that mediates many downstream effects such as vasodilation, neurotransmission, and calcium homeostasis. Considering the functions of cGMP, inhibition of PDE5 has been established to have several therapeutic effects in disease conditions such as cancer, cardiovascular diseases and Alzheimer's disease. Consequently, many PDE5 inhibitors were developed but with severe adverse effects such as non-arteritic anterior ischemic optic neuropathy (NAION), priapism, etc.

TBD-Mediated Diastereoselective Access to Functionalized 3-Alkenyl-2-oxindoles via the Tandem Reaction of Isatins and Allenoates.

The 1,5,7-triazabicyclo[4.4.0]dec-5-ene-mediated tandem reaction of easily accessible isatins and allenoates to functionalized 3-alkenyl-2-oxindoles is disclosed.

Design and discovery of carboxamide-based pyrazole conjugates with multifaceted potential against Triple-Negative Breast cancer MDA-MB-231 cells.

We report the design, synthesis, and validation of carboxamide-based pyrazole and isoxazole conjugates with a multifaceted activity against Breast Cancer Cell Line MDA-MB-231. The study established that amongst the series, N-(3,5-bis(trifluoromethyl)benzyl)-3-(3,4,5-trimethoxyphenyl)-1H-pyrazole-5-carboxamide (5g) exhibits the highest potency in inhibiting Breast Cancer Cell Line MDA-MB-231 with an IC value of 15.08 ± 0.

Ligand-Based Pharmacophoric Design and Anti-inflammatory Evaluation of Triazole Linked Semisynthetic Labdane Conjugates.

This study employed a ligand-based pharmacophoric approach to design and synthesize 33 novel semisynthetic labdane-appended triazolyl isatins to discover potential anti-inflammatory agents. The anti-inflammatory efficacy of the derivatives was evaluated by their ability to inhibit the production of NO, TNF-α, and IL-6, in lipopolysaccharide-induced RAW264.7 macrophages.

Linker-Based Pharmacophoric Design and Semisynthesis of Labdane Conjugates Active against Multi-Faceted Inflammatory Targets.

Prolonged inflammation leads to the genesis of various inflammatory diseases such as atherosclerosis, cancer, inflammatory bowel disease, Alzheimer's, etc. The uncontrolled inflammatory response is characterized by the excessive release of pro-inflammatory mediators such as nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1alpha (IL-1α), and inflammatory enzymes such as cyclooxygenase-2 (COX-2). Hence, the downregulation of these inflammatory mediators is an active therapy to control aberrant inflammation and tissue damage.

Diastereoselective Synthesis of Fused Tricyclic Pyridopyrimidines via Tandem Cyclization of Allenoates and Cyclic Amidines.

The tandem cyclization of easily accessible allenoates and cyclic amidines for the synthesis of functionalized tricyclic pyridopyrimidines is reported herein. The annulation featured a broad substrate scope with good functional group tolerance under very mild conditions (35 examples, 32-85% yields). The pyridopyrimidines were obtained in a very short reaction time (1 min), at room temperature, under neat conditions, which offers an alternative way to the sustainable synthesis of functionalized pyridopyrimidines.

Palladium Nanoparticles Grafted onto Phytochemical Functionalized Biochar: A Sustainable Nanozyme for Colorimetric Sensing of Glucose and Glutathione.

The devising and development of numerous enzyme mimics, particularly nanoparticles and nanomaterials (nanozymes), have been sparked by the inherent limitations imposed by natural enzymes. Peroxidase is one of the enzymes that is extensively utilized in commercial, medical, and biological applications because of its outstanding substrate selectivity. Herein, we present palladium nanoparticles grafted on (jackfruit) seed-derived biochar (BC-AHE@Pd) as a novel nanozyme to imitate peroxidase activity en route to the rapid and colorimetric detection of HO, exploiting -phenylenediamine as a peroxidase substrate.

DBU-Catalyzed Diastereo/Regioselective Access to Highly Substituted Spiro-oxetane Oxindoles Ring Annulation of Isatins and Allenoates.

A facile and efficient method for the diastereo/regioselective synthesis of highly functionalized spiro-oxetane oxindoles has been described. The 1,8-diazabicyclo[5.4.

Ethnobotanical significance of medicinal plants: Beta-amyloid and tau aggregation inhibitors against Alzheimer's disease.

Among the various neurodegenerative disorders, Alzheimer's disease (AD) is identified as one of primary causes of dementia in the elderly, which progresses slowly leading to cognitive decline and ability to function independently. Although various pathological mechanisms have been proposed, the exact mechanism is not yet elucidated. Numerous processes such as old age, mitochondrial dysfunction, and genetics lead to the aggregation of beta-amyloid (Aβ) as amyloid plaques and tau proteins as neurofibrillary tangles in the neurons leading to their death and destruction, finally leading to AD.

Investigation of embelin synthetic hybrids as potential COVID-19 and COX inhibitors: Synthesis, spectral analysis, DFT calculations and molecular docking studies.

Embelin (2, 5-dihydroxy-3-undecyl-1,4-benzoquinone), a benzoquinone isolated from fruits of Embelia ribes has miscellaneous biological potentials including; anticancer, anti-inflammation, antibiotic, and anti-hyperglycemic activities. Also, embelin down-regulates the overexpression of inflammatory pathways like NF-kB, TACE, TNF-α, and other cytokines. Furthermore, embelin fascinated synthetic interest as a pharmacologically active compound.

Multicomponent Synthesis of Spiro-dihydropyridine Oxindoles Cascade Spiro-cyclization of Knoevenagel/Aza-Michael Adducts.

An efficient, straightforward, and one-pot synthesis of biologically relevant spiro-dihydropyridine oxindoles was described readily available isatin, malononitrile, allenoate, and amines. The metal/organocatalyst-free, EtN-mediated reaction proceeds cascade spiro-cyclization of generated Knoevenagel/aza-Michael adducts. The reaction has great flexibility over electron-rich and electron-poor substituents affording desired products in good to excellent yields.

Comprehensive Review on Medicinal Applications of Coumarin-Derived Imine-Metal Complexes.

Coumarins are fused six-membered oxygen-containing benzoheterocycles that join two synthetically useful rings: α-pyrone and benzene. A survey of the literature shows that coumarins and their metal complexes have received great interest from synthetic chemists, medicinal scientists, and pharmacists due to their wide spectrum of biological applications. For instance, coumarin and its derivatives have been used as precursors to prepare a large variety of medicinal agents.

Marine Based Natural Products: Exploring the Recent Developments in the Identification of Antimicrobial Agents.

The marine ecosystem is the less explored, biologically diverse, and vastest resource to discover novel antimicrobial agents. In recent decades' antimicrobial drugs are losing their effectiveness due to the growing resistance among pathogens, which causes diseases to have considerable death rates across the globe. Therefore, there is a need for the discovery of new antibacterials that can reach the market.

Antibacterial natural products from microbial and fungal sources: a decade of advances.

Throughout the ages the world has witnessed the outbreak of many infectious diseases. Emerging microbial diseases pose a serious threat to public health. Increasing resistance of microorganisms towards the existing drugs makes them ineffective.

An insight into the recent developments in anti-infective potential of indole and associated hybrids.

Prevention, accurate diagnosis, and effective treatment of infections are the main challenges in the overall management of infectious diseases. The best example is the ongoing SARs-COV-2(COVID-19) pandemic; the entire world is extremely worried about at present. Interestingly, heterocyclic moieties provide an ideal scaffold on which suitable pharmacophores can be designed to construct novel drugs.

Correction: I/TBHP mediated diastereoselective synthesis of spiroaziridines.

Correction for 'I/TBHP mediated diastereoselective synthesis of spiroaziridines' by Kizhakkan Thiruthi Ashitha , , 2020, , 1588-1593, DOI: 10.1039/C9OB02711D.

Zerumin A attenuates the inflammatory responses in LPS-stimulated H9c2 cardiomyoblasts.

Zerumin A (ZA) is one of the potential components of Curcuma amada rhizomes, and it has been shown to possess a variety of pharmacological activities. This study deals with the beneficial activity of ZA in lipopolysaccharide (LPS)-stimulated inflammation in H9c2 cardiomyoblasts. Herein, H9c2 cells were preincubated with ZA for 1 h and stimulated with LPS for 24 h.

Anti-hyperlipidemic potential of natural product based labdane-pyrroles via inhibition of cholesterol and triglycerides synthesis.

Hyperlipidemia is the clinical condition where blood has an increased level of lipids, such as cholesterol and triglycerides. Therefore controlling hyperlipidemia is considered to be a protective strategy to treat many associated diseases. Thus, a novel natural product derived pyrrole, and pyrazole-(E)-Labda-8(17),12-diene-15,16-dial conjugates with cholesterol and triglycerides synthesis inhibition potential was designed through scaffold hopping approach and synthesized via one-pot selective cycloaddition.

Base-enabled access to diastereoselective spirofuran oxindoles and γ-functionalized allenoates.

Base assisted divergent reactivity of isatins and allenoates has been achieved, which afforded diastereoselective spirofuran oxindoles and γ-functionalized allenoates. The DBU mediated Morita-Baylis-Hillman (MBH) reaction followed by the cascade annulation through the stabilized β-ammonium enolate intermediate led to the spiro-framework, wherein DABCO furnished the γ-functionalized allenoates. The protocol offers access to biologically relevant functionalized oxindole scaffolds with an excellent substrate scope under mild reaction conditions.

Advanced glycation end-products (AGE) trapping agents: Design and synthesis of nature inspired indeno[2,1-c]pyridinones.

Advanced glycation end products (AGEs) are implicated to be the key players in most of the diabetic complications. The AGE's interfere with the proteins heterogeneously, thereby rendering denaturation and the consequent loss of function and accumulation. Thus, a novel natural product inspired indeno[2,1-c]pyridinone (4a-4ad) molecular templates with AGE's trapping potential was designed through scaffold hopping approach and synthesized via facile two-step synthetic route.

Rapid Visual Detection of Amines by Pyrylium Salts for Food Spoilage Taggant.

Amines are ubiquitous in biological world, but are toxic and harmful in nature. Detection of biogenic amines that are released from spoiled seafood, meat, or dairy products is an important task to maintain the quality and safety of these packaged foods. To this endeavor, herein we report pyrylium salts that are capable of sensing various amines by rapid change of fluorescence color or intensity.

Synthesis of 1,2,4-Trisubstituted-(1)-imidazoles through Cu(OTf)-/I-Catalyzed C-C Bond Cleavage of Chalcones and Benzylamines.

1,2,4-Trisubstituted-(1)-imidazoles have been synthesized by the Cu(OTf)- and I-catalyzed unusual C-C bond cleavage of chalcones and benzylamines. After the α,β-unsaturated C-C bond cleavage, the β-portion is eliminated from the reaction. Various aryl- and heteroaryl-substituted chalcones and benzylamines were well tolerated in this unusual transformation to yield the trisubstituted-(1)-imidazoles.

Discovery of Natural Product Derived Labdane Appended Triazoles as Potent Pancreatic Lipase Inhibitors.

Obesity contributes to the genesis of many metabolic disorders including dyslipidemia, coronary heart disease (CHD), nonalcoholic fatty liver, type 2 diabetes, etc. Pancreatic lipase plays a vital role in food fat digestion and absorption. Therefore, to control obesity, inhibition of pancreatic lipase is the active therapy.

A mini library of novel triazolothiadiazepinylindole analogues: synthesis, antioxidant and antimicrobial evaluations.

A new series of novel triazolothiadiazepinylindole analogues were synthesized with an aim to examine possible antioxidant and antimicrobial activities. The titled compounds (3a-z) were obtained in good yield by reacting 5-(5-substituted-3-phenyl-1H-indol-2-yl)-4-amino-4H-1,2,4-triazole-3-thiols 1a-c with 3-(2,5-disubstituted-1H-indol-3-yl)-1(4-substituted phenyl)prop-2-en-1-ones 2a-i. All the newly synthesized compounds were characterized by IR, (1)H NMR, mass spectroscopic and analytical data.