Review on recent advances in cellulose nanofibril based hybrid aerogels: Synthesis, properties and their applications.

With the depletion of fossil fuels and growing environmental concerns, the modernized era of technology is in desperate need of sustainable and eco-friendly materials. The industrial sector surely has enough resources to produce cost-effective, renewable, reusable, and sustainable raw materials. The family of very porous solid materials known as aerogels has a variety of exceptional qualities, such as high porosity, high specific surface area, ultralow density, and superior thermal, acoustic, and dielectric properties. As a result, aerogels have the potential to be used for many different purposes, such as absorbents, supercapacitors, energy storage, and catalytic supports. Recently, cellulose nanofibril (CNF) aerogels have attracted remarkable attention for their large-scale utilization because of their high absorption capacity, low density, biodegradability, large surface area, high porosity, and biocompatibility. Recent advancements have confirmed that CNF-based hybrid aerogels can be proposed as the most privileged and promising novel material in various applications. This comprehensive review highlights the recent reports of the CNF-based hybrid aerogels, including their properties and frequent preparation approaches, in addition to their new applications in the areas of fire retardant, water and oil separation, supercapacitors, environmental, and CO2 capture. It is also assumed that this article will promote additional investigation and establish innovative capabilities to enhance novel CNF-based hybrid aerogels with new and exciting applications.

Recent Progress in the Multicomponent Synthesis of Pyran Derivatives by Sustainable Catalysts under Green Conditions.

Pyrans are one of the most significant skeletons of oxygen-containing heterocyclic molecules, which exhibit a broad spectrum of medicinal applications and are constituents of diverse natural product analogues. Various biological applications of these pyran analogues contributed to the growth advances in these oxygen-containing molecules. Green one-pot methodologies for synthesising these heterocyclic molecules have received significant attention. This review focuses on the recent developments in synthesising pyran ring derivatives using reusable catalysts and emphasises the multicomponent reaction strategies using green protocols. The advantages of the catalysts in terms of yields, reaction conditions, and recyclability are discussed.

Multicomponent reaction for the synthesis of new 1,3,4-thiadiazole-thiazolidine-4-one molecular hybrids as promising antidiabetic agents through α-glucosidase and α-amylase inhibition.

A simple and efficient protocol was developed to synthesize a new library of thiazolidine-4-one molecular hybrids (4a-n) via a one-pot multicomponent reaction involving 5-substituted phenyl-1,3,4-thiadiazol-2-amines, substituted benzaldehydes and 2-mercaptoacetic acid. The synthesized compounds were evaluated in vitro for their antidiabetic activities through α-glucosidase and α-amylase inhibition as well as their antioxidant and antimicrobial potentials. Compound 4e exhibited the most promising α-glucosidase and α-amylase inhibition with an IC50 value of 2.59 µM, which is ~1.5- and 14-fold superior as compared to the standard inhibitor acarbose. Structure-activity relationship (SAR) analysis revealed that the nature and position of substituents on the phenyl rings had a significant effect on the inhibitory potency.

Advances in Pyranopyrazole Scaffolds' Syntheses Using Sustainable Catalysts-A Review.

Heterogeneous catalysis plays a crucial role in many chemical processes, including advanced organic preparations and the design and synthesis of new organic moieties. Efficient and sustainable catalysts are vital to ecological and fiscal viability. This is why green multicomponent reaction (MCR) approaches have gained prominence. Owing to a broad range of pharmacological applications, pyranopyrazole syntheses (through the one-pot strategy, employing sustainable heterogeneous catalysts) have received immense attention. This review aimed to emphasise recent developments in synthesising nitrogen-based fused heterocyclic ring frameworks, exploring diverse recyclable catalysts. The article focused on the synthetic protocols used between 2010 and 2020 using different single, bi- and tri-metallic materials and nanocomposites as reusable catalysts. This review designated the catalysts' efficacy and activity in product yields, reaction time, and reusability. The MCR green methodologies (in conjunction with recyclable catalyst materials) proved eco-friendly and ideal, with a broad scope that could feasibly lead to advancements in organic synthesis.

A Facile and Catalyst-Free Microwave-Promoted Multicomponent Reaction for the Synthesis of Functionalised 1,4-Dihydropyridines With Superb Selectivity and Yields.

We report a highly efficient green protocol for developing a novel library of 1,2,4-triazole-tagged 1,4-dihydropyridine analogs through the one-pot process from the four-component fusion of the 1H-1,2,4-triazol-3-amine with different chosen aldehydes, diethyl acetylenedicarboxylate, and active methylene compounds in a water medium under microwave irradiation and catalyst-free conditions. Excellent yields (94-97%) of the target products were achieved with high selectivity with a short reaction time (<12 min) at room temperature. The structures of the synthesized pyrimidine analogs were established by NMR and HRMS spectroscopic analysis. Simple workup, impressive yields, no column chromatography, green solvent, rapid reaction, and excellent functional group tolerance are the benefits of this protocol.

Recent Progresses in the Multicomponent Synthesis of Dihydropyridines by Applying Sustainable Catalysts Under Green Conditions.

The synthesis of dihydropyridines, valuable molecules with diverse therapeutic properties, using eco-friendly heterogeneous catalysts as a green alternative received significant consideration. By selecting appropriate precursors, these compounds can be readily modified to induce the desired properties in the target product. This review focused on synthesising diverse dihydropyridine derivatives in single-pot reactions using magnetic, silica, and zirconium-based heterogeneous catalytic systems. The monograph describes preparation techniques for various catalyst materials in detail. It covers facile and benign magnetic, silica, zirconium-based, and ionic liquid catalysts, exhibiting significant efficacy and consistently facilitating excellent yields in short reaction times and in a cost-effective way. Most of the designated protocols employ Hantzsch reactions involving substituted aldehydes, active methylene compounds, and ammonium acetate. These reactions presumably follow Knoevenagel condensation followed by Michael addition and intra-molecular cyclisation. The multicomponent one-pot protocols using green catalysts and solvents have admirably increased the product selectivity and yields while minimising the reaction time. These sustainable catalyst materials retain their viability for several cycles reducing the expenditure are eco-friendly.

Synthesis of 1H-1,2,3-Triazole-Linked Quinoline-Isatin Molecular Hybrids as Anti-Breast Cancer and Anti-Methicillin-Resistant Staphylococcus aureus (MRSA) Agents.

BACKGROUND: The persistence of breast cancer as the leading cause of mortality among women, coupled with drug resistance to tamoxifen, the standard endocrine therapy for the disease, exacts continuous attention. To this effect, molecular hybridisation offers an attractive route to drugs with improved bioactivity profiles. OBJECTIVE: The primary goal of this study was to examine the potential of 1H-1,2,3-triazole linked quinolineisatin molecular hybrids as drug candidates against breast cancer and Methicillin-Resistant Staphylococcus aureus (MRSA) cells. METHODS: The quinoline-isatin hybrids were synthesised via click chemistry-mediated molecular hybridisation strategy. Anti-breast cancer activity was determined in 3-(4,5-dimethylthiazol-z-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using Estrogen-Responsive (ER+) MCF-7 and MDA-MB-231 (Triple-Negative Breast Cancer -TNBC) cells, while antimicrobial efficacy was established via the broth dilution method. Also, the toxicity profile of potent compounds to non-cancerous cells was determined using human embryonic kidney cells (HEK293) and human Red Blood Cells (hRBCs). In silico techniques were employed to predict the druglike properties of potent compounds and understand their binding modes with Estrogen Receptor alpha (ERα). RESULTS: Compounds 7g-i exhibited the strongest cytotoxicity to MCF-7 cells with IC50 values of 23.54, 23.66, and 32.50µM, respectively. Interestingly, compound 7h also emerged as the best drug candidate against MDAMB- 231 and MRSA cells with IC50=71.40µM and MIC80=27.34µM, respectively. Structure-activity relationship analysis revealed that quinoline-2-carbaldehyde and 5,7-disubstituted isatin moieties confer desirable potency. These compounds showed no significant cytotoxic or haemolytic effects on HEK293 or hRBCs in vitro at their active concentrations; hence, eliciting their selectivity for cancer cells. In silico studies also presented the drugability of potent compounds and the likely structural features interacting with amino acid residues at the ligandbinding domain of ERα. CONCLUSION: These results suggest that the identified 1H-1,2,3-triazole-linked quinoline-isatin hybrids are viable chemotypes that can be adopted as templates for the development of new anti-breast cancer and anti-MRSA agents.

Synthesis, antimicrobial evaluation, and in silico studies of quinoline-1H-1,2,3-triazole molecular hybrids.

Antimicrobial resistance has become a significant threat to global public health, thus precipitating an exigent need for new drugs with improved therapeutic efficacy. In this regard, molecular hybridization is deemed as a viable strategy to afford multi-target-based drug candidates. Herein, we report a library of quinoline-1H-1,2,3-triazole molecular hybrids synthesized via copper(I)-catalyzed azide-alkyne [3 + 2] dipolar cycloaddition reaction (CuAAC). Antimicrobial evaluation identified compound 16 as the most active hybrid in the library with a broad-spectrum antibacterial activity at an MIC80 value of 75.39 µM against methicillin-resistant S. aureus, E. coli, A. baumannii, and multidrug-resistant K. pneumoniae. The compound also showed interesting antifungal profile against C. albicans and C. neoformans at an MIC80 value of 37.69 and 2.36 µM, respectively, superior to fluconazole. In vitro toxicity profiling revealed non-hemolytic activity against human red blood cells (hRBC) but partial cytotoxicity to human embryonic kidney cells (HEK293). Additionally, in silico studies predicted excellent drug-like properties and the importance of triazole ring in stabilizing the complexation with target proteins. Overall, these results present compound 16 as a promising scaffold on which other molecules can be modeled to deliver new antimicrobial agents with improved potency.

Synthesis of indole-tethered [1,3,4]thiadiazolo and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids as anti-pancreatic cancer agents.

New indole-tethered [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one (8a-j) and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids (9a-e) were synthesized using [4+2] cycloaddition reactions of functionalized 1,3-diazabuta-1,3-dienes with indole-ketenes. All molecular hybrids were structurally characterized by spectroscopic techniques (IR, NMR, and HRMS) and screened for their anti-pancreatic cancer activity in vitro. The [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids (9a-e) showed stronger anti-pancreatic cancer activity than the [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one hybrids (8a-j) against the PANC-1 cell line. Compound 9d bearing an ortho-chlorophenyl moiety emerged as the most potent anti-pancreatic cancer agent with an IC50 value of 7.7 ± 0.4 µM, much superior to the standard drug Gemcitabine (IC50 > 500 µM). The discovery of these [1,3,4]thiadiazolo and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids elicits their potentials as pursuable candidates for pancreatic cancer chemotherapy.

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications.

The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

Green synthesis and characterisation of novel [1,3,4]thiadiazolo/benzo[4,5]thiazolo[3,2-a]pyrimidines via multicomponent reaction using vanadium oxide loaded on fluorapatite as a robust and sustainable catalyst.

We synthesised materials with different loadings of vanadia on fluorapatite (V2O5/FAp), fully characterised their structural properties using various spectral techniques including TEM, BET, XRD, FT-IR, SEM and EDX and assessed their prowess as catalysts. The 2.5% V2O5/FAp exhibited excellent activity for the synthesis of novel [1,3,4]thiadiazolo[3,2-a]pyrimidines and benzo[4,5]thiazolo[3,2-a]pyrimidines. The one-pot three-component fusion reaction between chosen substrates of 1,3,4-thiadiazole-amines or 2-amino-benzothiazole, aldehydes and active methylene compounds in ethanol solvent at room temperature gave an excellent yield of products (90-97%) in a swift reaction (25-30 min). The advantages of this protocol are rapid synthesis, mild reaction conditions, green solvent, easy work-up, eco-friendliness, reusability of catalyst and no need for column chromatography.

Green synthesis and characterization of novel 1,2,4,5-tetrasubstituted imidazole derivatives with eco-friendly red brick clay as efficacious catalyst.

Use of cheaper and recyclable materials contributes positively to economic growth with environmental sustainability. We report the prospect of utilizing red brick clay as catalyst, which exhibited excellent activity in rapid one-pot four-component condensation of 1,2,4,5-tetrasubstituted imidazoles with high conversion and yields (91-96%) in aqueous medium at 60 °C in short reaction times (25-40 min). The red brick clay material was fully characterized by XRD, FT-IR, SEM, TEM, EDX and BET analyses. Red brick clay consisted of oxides of Si (20.38%), Fe (19.55%), Al (14.30%) and minor amounts of Ca (3.60%) and Mg (1.68%). The slate-like-shaped structure morphology and flaky appearance of inexpensive solid clay material proved competent material for the synthesis of 15 novel 1,2,4,5-tetrasubstituted imidazole derivatives. In addition, the advantages of the eco-friendly method are non-toxicity and re-usability of the catalyst. Reaction offers 78% atom economy and 84% carbon capture.

Efficient synthesis of novel pyrazole-linked 1,2,4-triazolidine-3-thiones using bismuth on zirconium oxide as a recyclable catalyst in aqueous medium.

The Bi2O3 loading on ZrO2 as heterogeneous catalyst was established as an extremely efficient catalyst for the synthesis of a series of novel 5-(1-(2,4-dinitrophenyl)-3-substituted-phenyl-1H-pyrazol-4-yl)-1,2,4-triazolidine-3-thione derivatives (3a-o) with high yields (90-96%) by reaction of 1-(2,4-dinitrophenyl)-3-substituted-phenyl-1H-pyrazole-4-carbaldehydes and thiosemicarbazide using water as a greener solvent at 80 °C within 30-45 min. Materials with different percentages of Bi2O3 on ZrO2 were prepared by simple wet impregnation method. The synthesized material has been characterized by various techniques (XRD, TEM, SEM, BET). 2.5% Bi2O3/ZrO2 proved superior catalyst. The Bi2O3/ZrO2 catalyst is easily recoverable and reused up to sixth run with no loss of activity. Excellent yields, short reaction time, avoidance of hazardous solvents, and no need for chromatographic purifications are the proven advantages.

Therapeutic significance of ß-glucuronidase activity and its inhibitors: A review.

The emergence of disease and dearth of effective pharmacological agents on most therapeutic fronts, constitutes a major threat to global public health and man's existence. Consequently, this has created an exigency in the search for new drugs with improved clinical utility or means of potentiating available ones. To this end, accumulating empirical evidence supports molecular target therapy as a plausible egress and, ß-glucuronidase (ßGLU) - a lysosomal acid hydrolase responsible for the catalytic deconjugation of ß-d-glucuronides has emerged as a viable molecular target for several therapeutic applications. The enzyme's activity level in body fluids is also deemed a potential biomarker for the diagnosis of some pathological conditions. Moreover, due to its role in colon carcinogenesis and certain drug-induced dose-limiting toxicities, the development of potent inhibitors of ßGLU in human intestinal microbiota has aroused increased attention over the years. Nevertheless, although our literature survey revealed both natural products and synthetic scaffolds as potential inhibitors of the enzyme, only few of these have found clinical utility, albeit with moderate to poor pharmacokinetic profile. Hence, in this review we present a compendium of exploits in the present millennium directed towards the inhibition of ßGLU. The aim is to proffer a platform on which new scaffolds can be modelled for improved ßGLU inhibitory potency and the development of new therapeutic agents in consequential.

A comparison between observed and DFT calculations on structure of 5-(4-chlorophenyl)-2-amino-1,3,4-thiadiazole.

The crystal and molecular structure of 5-(4-chlorophenyl)-2-amino-1,3,4-thiadiazole 3 was reported, which was characterized by various spectroscopic techniques (FT-IR, NMR and HRMS) and single-crystal X-ray diffraction. The crystal structure 3 (C8H6ClN3S) crystallized in the orthorhombic space group Pna21 and the unit cell consisted of 8 asymmetric molecules. The unit cell parameters were a = 11.2027(2) Å, b = 7.6705(2) Å, c = 21.2166(6) Å, α = ß = γ = 90°, V = 1823.15(8) Å3, Z = 8. In addition, the structural geometry (bond lengths, bond angles, and torsion angles), the electronic properties of mono and dimeric forms of compound 3 were calculated by using the density functional theory (DFT) method at B3LYP level 6-31+ G(d,p), 6-31++ G(d,p) and 6-311+ G(d,p) basis sets in ground state. A good correlation was found (R2 = 0.998) between the observed and theoretical vibrational frequencies. Frontier molecular orbitals (HOMO and LUMO) and Molecular Electrostatic Potential map of the compound was produced by using the optimized structures. The NBO analysis was suggested that the molecular system contains N-H…N hydrogen bonding, strong conjugative interactions and the molecule become more polarized owing to the movement of π-electron cloud from donor to acceptor. The calculated structural and geometrical results were in good rational agreement with the experimental X-ray crystal structure data of 1,3,4-thiadiazol-2-amine, 3. The compound 3 exhibited n→π* UV absorption peak of UV cutoff edge, and great magnitude of the first-order hyperpolarizability was observed. The obtained results suggest that compound 3 could have potential application as NLO material. Therefore, this study provides valuable insight experimentally and theoretically, for designing new chemical entities to meet the demands of specific applications.

Synthesis, computational studies and antiproliferative activities of coumarin-tagged 1,3,4-oxadiazole conjugates against MDA-MB-231 and MCF-7 human breast cancer cells.

A novel library of coumarin tagged 1,3,4 oxadiazole conjugates was synthesized and evaluated for their antiproliferative activities against MDA-MB-231 and MCF-7 breast cancer cell lines. The evaluation studies revealed that compound 9d was the most potent molecule with an IC50 value of <5 µM against the MCF-7 cell line. Interestingly, compounds 10b and 11a showed a similar trend with lower inhibitory concentration (IC50 = 7.07 µM), in Estrogen Negative (ER-) cells than Estrogen Positive (ER+) cells. Structure-activity relationship (SAR) studies revealed that conjugates bearing benzyl moieties (9b, 9c and 9d) had superior activities compared to their alkyl analogues. The most potent compound 9d showed ∼1.4 times more potent activity than tamoxifen against MCF-7 cell line; while the introduction of sulfone unit in compounds 11a, 11b and 11c resulted in significant cytotoxicity against both MCF-7 and MDA-MB-231 cell lines. These results were further supported by docking studies, which revealed that the stronger binding affinity of the synthesized conjugates is due to the presence of sulfone unit attached to the substituted benzyl moiety in their pharmacophores.

Current anti-diabetic agents and their molecular targets: A review.

Diabetes mellitus is a medical condition characterized by the body's loss of control over blood sugar. The frequency of diagnosed cases and consequential increases in medical costs makes it a rapidly growing chronic disease that threatens human health worldwide. In addition, its unnerving statistical projections are perilous to both the economy of the nation and man's life expectancy. Type-I and type-II diabetes are the two clinical forms of diabetes mellitus. Type-II diabetes mellitus (T2DM) is illustrated by the abnormality of glucose homeostasis in the body, resulting in hyperglycemia. Although significant research attention has been devoted to the development of diabetes regimens, which demonstrates success in lowering blood glucose levels, their efficacies are unsustainable due to undesirable side effects such as weight gain and hypoglycemia. Over the years, heterocyclic scaffolds have been the basis of anti-diabetic chemotherapies; hence, in this review we consolidate the use of bioactive scaffolds, which have been evaluated for their biological response as inhibitors against their respective anti-diabetic molecular targets over the past five years (2012-2017). Our investigation reveals a diverse target set which includes; protein tyrosine phosphatase 1 B (PTP1B), dipeptidly peptidase-4 (DPP-4), free fatty acid receptors 1 (FFAR1), G protein-coupled receptors (GPCR), peroxisome proliferator activated receptor-γ (PPARγ), sodium glucose co-transporter-2 (SGLT2), α-glucosidase, aldose reductase, glycogen phosphorylase (GP), fructose-1,6-bisphosphatase (FBPase), glucagon receptor (GCGr) and phosphoenolpyruvate carboxykinase (PEPCK). This review offers a medium on which future drug design and development toward diabetes management may be modelled (i.e. optimization via structural derivatization), as many of the drug candidates highlighted show promise as an effective anti-diabetic chemotherapy.

Recent advances (2015-2016) in anticancer hybrids.

In spite of the development of a large number of novel anticancer drugs over the years, Cancer remains as a prominent cause of death, worldwide. Numerous drugs that are currently in clinical practice have developed multidrug resistance along with fatal side effects. Therefore, the utilization of single-target therapy is incapable of providing an effective control on the malignant process. Molecular hybridization, involving a combination of two or more pharmacophores of bioactive scaffolds to generate a single molecular architecture with improved affinity and activity, in comparison to their parent molecules, has emerged as a promising strategy in recent drug discovery research. Hybrid anticancer drugs are of great therapeutic interests since they can potentially overcome most of the pharmacokinetic drawbacks encountered with conventional anticancer drugs. Strategically, the design of anticancer drugs involved the blending or linking of an anticancer drug with another anticancer drug or a carrier molecule which can efficiently target cancer cells with improved biological potential. Major advantages of hybrid anticancer drugs involved increased specificity, better patient compliance, and lower side effects along with reduction in chemo-resistance. The successful utilization of this technique in design and synthesis of novel anticancer hybrids has been well illustrated and documented in the literature. The purpose of the present review article will be to provide an emphasis on the recent developments (2015-16) in anticancer hybrids with insights into their structure-activity relationship (SAR) and mechanism of action.

A Review of Recent Advancements in Anti-tubercular Molecular Hybrids.

Tuberculosis (TB) accounts for millions of deaths worldwide every year. Diverse survival strategies adopted by Mycobacterium tuberculosis (Mtb) have substantially hindered the existing anti-TB regimen thereby leading to multidrug-resistant (MDR) and extremely drug-resistant (XDR) strains of TB. The steady decrease in current antibiotics' efficacy against these adversities is an indicator that their adequate replenishment in future is almost impossible, placing society on the precipice of a catastrophe. Over the past many years, researchers have been continuously generating new armamentarium of anti- TB drugs by tailoring the properties of available drugs or designing completely new agents. One of these emerging and successful synthetic techniques is molecular hybridization (MH) that involves the integration of different pharmacophoric subunits to form a new prototype with the ability to be recognized by multiple receptors. In most cases, the resultant conjugates have been reported to exhibit superior biological activity profiles relative to their parent molecules which is attributed to their different or dual modes of action. Accordingly, several new effective anti-TB scaffolds have been synthesized using this approach, and are well cited in literature. In this review, we provide a summarized account of the chemical strategies optimistically focused to develop new molecular assemblies for TB via MH approaches. Additionally, the structure activity relationships revealed from different biological assays is systematically discussed.