Cardiovascular diseases display etiological and seasonal trend in human population: Evidence from seasonal cardiovascular comorbid diseases (SCCD) index.

Seasonal changes in the human cardiovascular system are known to play an important role in the onset of many diseases. Confounding variables include behavioral and environmental factors; failing to address such variables makes measuring the true temporal impact of these diseases difficult. On the other hand, numerous clinical studies imply that only specific groups of people are more seasonal sensitive and that their maladaptation might contribute to various illnesses. As a result, it is critical to evaluate the etiological and seasonal sensitive patterns of cardiovascular diseases (CVD), which impact the majority of the human population. The hypothesis for this study formulated that cardiovascular and associated illnesses had substantial connections with seasonal and etiological variations. Thus in the present study, 4519 systematic screen-eligible studies were analyzed using data mining to uncover 852 disease association relationships between cardiovascular and associated disorders. A disease ontology-based semantic similarity network (DSN) analysis was performed to narrow down the identified CVDs. Further, topological analysis was used to predict the seven CVDs, including myocardial infarction (MI), in three clusters. Following that, Mann-Kendall and Cox-Stuart analyses were used to investigate the seasonal sensitivity and temporal relationship of these seven CVDs. Finally, temporal relationships were confirmed using LOESS and TBATS, as well as seasonal breakdown utilizing autocorrelation and fast Fourier transform results. The study provides indirect evidence of a severe etiological association among the three cardiovascular diseases, including MI, atrial fibrillation, and atherosclerosis, which are winter season sensitive in most of the world population. Hypertension has two seasonal falls and peaks due to its seasonal nature, that is, summer and winter hypertension. While, heart failure was also identified, with minor temporal trends. Hence, all five diseases could be classified as seasonal cardiovascular comorbid diseases (SCCD). Furthermore, these diseases could be studied for potential common risk factors such as biochemical, genetic, and physiological factors.

Thiazolidin-2,4-Dione Scaffold: An Insight into Recent Advances as Antimicrobial, Antioxidant, and Hypoglycemic Agents.

Heterocyclic compounds containing nitrogen and sulfur, especially those in the thiazole family, have generated special interest in terms of their synthetic chemistry, which is attributable to their ubiquitous existence in pharmacologically dynamic natural products and also as overwhelmingly powerful agrochemicals and pharmaceuticals. The thiazolidin-2,4-dione (TZD) moiety plays a central role in the biological functioning of several essential molecules. The availability of substitutions at the third and fifth positions of the Thiazolidin-2,4-dione (TZD) scaffold makes it a highly utilized and versatile moiety that exhibits a wide range of biological activities. TZD analogues exhibit their hypoglycemic activity by improving insulin resistance through PPAR-γ receptor activation, their antimicrobial action by inhibiting cytoplasmic Mur ligases, and their antioxidant action by scavenging reactive oxygen species (ROS). In this manuscript, an effort has been made to review the research on TZD derivatives as potential antimicrobial, antioxidant, and antihyperglycemic agents from the period from 2010 to the present date, along with their molecular mechanisms and the information on patents granted to TZD analogues.

2-AZETIDINONE DERIVATIVES: SYNTHESIS, ANTIMICROBIAL, ANTICANCER EVALUATION AND QSAR STUDIES.

A series of 2-azetidinone derivatives was synthesized from hippuric acid and evaluated for its in vitro antimicrobial and anticancer activities. Antimicrobial properties of the title compounds were investigated against Gram positive and Gram negative bacterial as well as fungal strains. Anticancer activity was performed against breast cancer (MCF7) cell lines. Antimicrobial activity results revealed that N-{2-[3-chloro-2-(2- chlorophenyl)-4-oxoazetidin-1-ylamino]-2-oxoethyl}benzamide (4) was found to be the most potent antimicrobial agent. Results of anticancer study indicated that the synthesized compounds exhibited average anticancer potential and N-[2-(3-chloro-2-oxo-4-styrylazetidin-1-ylamino)-2-oxoethyl]benzamide (17) was found to be most potent anticancer agent against breast cancer (MCF7) cell lines. QSAR models indicated that the antibacterial, antifungal and the overall antimicrobial activities of the synthesized compounds were governed by topological parameters, Balaban index (J) and valence zero and first order molecular connectivity indices (°χv and ¹χv).

SYNTHESIS, ANTIMICROBIAL, ANTICANCER EVALUATION AND QSAR STUDIES OF THIAZOLIDIN-4-ONE DERIVATIVES.

In this study, a novel series of 4-thiazolidinone derivatives (1-17) was synthesized and evaluated for its in vitro antimicrobial and anticancer potentials. N-(2-(5-(4-nitrobenzylidene)-2-(4-chlorophenyl)-4-oxothia- zolidin-3-ylamino)-2-oxoethyl) benzamide (7, pMICam = 1.86 µM/mL) was found to be the most active antimi- crobial agent. The anticancer study results demonstrated that N-(2-(5-(4-hydroxybenzylidene)-2-(4- methoxyphenyl)-4-oxothiazolidin-3-ylamino)-2-oxoethyl) benzamide (10, IC50 = 18.59 µM) was the most active anticancer agent. QSAR studies indicated the importance of topological parameter, Kier's α third order shape index (κα3) as well as electronic parameters, cosmic total energy (cos E) and energy of highest occupied molecular orbital (HOMO) in describing the antimicrobial activity of synthesized compounds.

Pharmacological potential of (L.) P. Royen (Sapodilla): a narrative review.

Herbal medicine is safe and effective in treating various diseases. Traditional herbal medicine plays a tremendous role in treatment of various diseases and accompanying complications, hence herbal medicine requires remarkable attention in further research for the development of numerous active formulations for treatment of health troubles. The plant needs special consideration for development and research of unidentified compound and characterization of novel active molecules that overcome multiple pathological abnormalities. The genus Manilkara contains 135 plants around the world. This overview discusses all the virtues of most important and commonly used plant Manilkara zapota (L.) P. Royen (M. zapota), also known as Sapodilla. M. zapota has various traditional beneficial effects in treatment of various diseases and disorders dating back to prehistoric times and used in ancient traditional system of herbal medicine.

Recent advances, challenges and updates on the development of therapeutics for malaria.

Malaria has developed as a serious worldwide health issue as a result of the introduction of resistant Plasmodium species strains. Because of the common chemo resistance to most of the existing drugs on the market, it poses a severe health problem and significant obstacles in drug research. Malaria treatment has evolved during the last two decades in response to Plasmodium falciparum drug sensitivity and a return of the disease in tropical areas. Plasmodium falciparum is now highly resistant to the majority of antimalarial drugs. The parasite resistance drew focus to developing novel antimalarials to combat parasite resistance. The requirement for many novel antimalarial drugs in the future year necessitates adopting various drug development methodologies. Different innovative strategies for discovering antimalarial drugs are now being examined here. This review is primarily concerned with the description of newly synthesized antimalarial compounds, i.e. Tafenoquine, Cipargamin, Ferroquine, Artefenomel, DSM265, MMV390048 designed to improve the activity of pure antimalarial enantiomers. In this review, we selected the representative malarial drugs in clinical trials, classified them with detailed targets according to their action, discussed the relationship within the human trials, and generated a summative discussion with prospective expectations.

An Understanding of Mechanism-Based Approaches for 1,3,4-Oxadiazole Scaffolds as Cytotoxic Agents and Enzyme Inhibitors.

The world's health system is plagued by cancer and a worldwide effort is underway to find new drugs to treat cancer. There has been a significant improvement in understanding the pathogenesis of cancer, but it remains one of the leading causes of death. The imperative 1,3,4-oxadiazole scaffold possesses a wide variety of biological activities, particularly for cancer treatment. In the development of novel 1,3,4-oxadiazole-based drugs, structural modifications are important to ensure high cytotoxicity towards malignant cells. These structural modification strategies have shown promising results when combined with outstanding oxadiazole scaffolds, which selectively interact with nucleic acids, enzymes, and globular proteins. A variety of mechanisms, such as the inhibition of growth factors, enzymes, and kinases, contribute to their antiproliferative effects. The activity of different 1,3,4-oxadiazole conjugates were tested on the different cell lines of different types of cancer. It is demonstrated that 1,3,4-oxadiazole hybridization with other anticancer pharmacophores have different mechanisms of action by targeting various enzymes (thymidylate synthase, HDAC, topoisomerase II, telomerase, thymidine phosphorylase) and many of the proteins that contribute to cancer cell proliferation. The focus of this review is to highlight the anticancer potential, molecular docking, and SAR studies of 1,3,4-oxadiazole derivatives by inhibiting specific cancer biological targets, such as inhibiting telomerase activity, HDAC, thymidylate synthase, and the thymidine phosphorylase enzyme. The purpose of this review is to summarize recent developments and discoveries in the field of anticancer drugs using 1,3,4-oxadiazoles.

Applications of Nanomedicine in Brain Tumor Therapy: Nanocarrierbased Drug Delivery Platforms, CChallenges, and Perspectives.

BACKGROUND: The most difficult kind of cancer to treat is brain cancer, which causes around 3% of all cancer-related deaths. The targeted delivery is improved with the use of technologies based on nanotechnology that are both safe and efficient. Because of this, there is now a lot of research being done on brain cancer treatments based on nanoformulations. OBJECTIVE: In this review, the author's primary aim is to elucidate the various nanomedicine for brain cancer therapy. The authors focus primarily on the advancement of nanotechnology in treating brain cancer (BC). This review article gives readers an up-to-date look at publications on sophisticated nanosystems in treating BC, including quantum dots (QDs), nanoparticles (NPs), polymeric micelles (PMs), dendrimers, and solid lipid nanoparticles (SLNs), among others. This article offers insight into the use of various nanotechnology-based systems for therapy as well as their potential in the future. This article also emphasizes the drawbacks of nanotechnology-based methods. Future perspectives for treating brain cancer using proteomics and biomimetic nanosystems are briefly discussed. CONCLUSION: In this review, we review several aspects of brain cancer therapy, including various nanomedicines, their challenges and future perspectives. Overall, this article gives a thorough overview of both the present state of brain cancer treatment options and the disease itself.

Synthesis, Anticancer, Antimicrobial and Antioxidant Potential of Novel 4-(Substituted phenyl-1,3,4-oxadiazol/thiadiazol-2-yl)-4-(4-substituted phenyl) Azetidin-2-One Derivatives.

By exploiting the ample biological potential of 1,3,4-oxadiazole/thiadiazole ring, 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one derivatives were prepared. Various substituted azetidin-2-one derivatives have been identified as immunostimulating and antimicrobial, as well as their antioxidant activity. 2-amino 1,3,4 oxadiazole/thiadiazole conjugates were synthesized by mixing semi/thio carbazides and sodium acetate with water and stirring well, followed by adding aldehydes in methanol at room temperature. Acetate (glacial) was used as the catalyst to produce Schiff's bases (intermediates) by treating substituted aldehydes with 2-amino 1,3,4 oxadiazole/thiadiazole(s). Using the mixture of triethylamine (dropwise) and chloroacetylchloride with vigorous stirring, 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one derivatives were prepared. The newly synthesized conjugates were evaluated for their anticancer potential using MCF-7 cell lines. Amoxicillin and fluconazole were used as reference drugs to determine their antimicrobial activity. Synthesized derivatives were evaluated for their antioxidant properties using 2-diphenyl-1-picrylhydrazyl (DPPH). In vitro cytotoxicity screening (MTTS assay) revealed that derivatives AZ-5, 9, 10, 14 and 19 demonstrated high efficacy with the percentage of inhibition at different concentration ranges (0.1 µM, 0.5 µM, 1 µM, 2 µM) of 89% to 94% µM as compared to doxorubicin as standard drug. The antimicrobial study indicated that compounds AZ-10, 19, and AZ-20 were found to have significant antimicrobial potential with MIC ranges of 3.34 µM to 3.71 µM in comparison to reference drugs having 4.29 µM to 5.10 µM. Based on antioxidant screening, most of the synthetic derivatives showed greater stability and effectiveness than the standard drug. According to the antioxidant screening, compounds AZ-5 and AZ-15 (IC50 = 45.02 µg/mL and 42.88 µg/mL, respectively) showed the greatest potency, as compared to ascorbic acid (IC50 = 78.63 µg/mL). Structure-activity relationship (SAR) studies of synthesized novel derivatives revealed that para-substituted halogen and nitro derivatives have remarkable potential against MCF-7 cancer cell lines and different microbial strains. Current evidence indicates that the synthesized derivatives may be promising candidates for use in the prevention and treatment of these infections. These synthesized compounds require further mechanism-based research to understand how they interact with the cells.

2-Substituted-3-(5-Substituted-1,3,4-oxadiazol/thiadiazol-2-yl) Thiazolidin-4-one Derivatives: Synthesis, Anticancer, Antimicrobial, and Antioxidant Potential.

In this innovative research, a novel series of thiazolidin-4-one analogues having a 1,3,4-oxadiazole/thiadiazole moiety were derived and the structures of all the newly obtained molecules were established using different physicochemical and analytical means (1H-NMR, FTIR, mass spectra, and elemental analyses). The synthesized molecules were then investigated for their antiproliferative, antimicrobial, and antioxidant potential. The cytotoxicity screening studies revealed that analogues D-1, D-6, D-15, and D-16 possessed comparable efficacy, within the IC50 range (1 to 7 µM), when taking doxorubicin as a reference drug (IC50 = 0.5 µM). The antimicrobial activity was assessed using different Gram-(+) and Gram-(-) bacterial and fungal strains and the results revealed that molecules D-2, D-4, D-6, D-19, and D-20 possessed potent activity against selective strains of microbes with MIC ranges of 3.58 to 8.74 µM. The antioxidant evaluation was performed using the DPPH assay and the screening results revealed that analogue D-16 was the most potent derivative (IC50 = 22.3 µM) when compared with the positive control, ascorbic acid (IC50 = 111.6 µM). Structure-activity relationship (SAR) studies of the synthesized novel derivatives revealed that para-substituted halogen and hydroxy derivatives have remarkable potential against the MCF-7 cancer cell line and antioxidant potential. Similarly, electron-withdrawing groups (Cl/NO2) and -donating groups at the para position possess moderate to promising antimicrobial potential.

Synthesis and characterization of (E)-N'-(substituted benzylidene)isonicotinohydrazide derivatives as potent antimicrobial and hydrogen peroxide scavenging agents.

A series of (E)-N'-(substituted benzylidene)isonicotinohydrazide derivatives were synthesized by coupling isoniazid with differently substituted aldehydes and benzophenones in the presence of absolute ethanol along with catalytic amount of glacial acetic acid. The structure of all the synthesized compounds were confirmed and characterized by using various spectral technique like IR, 1H NMR, 13C NMR and mass spectroscopy. All the synthesized compounds were evaluated for their antimicrobial activity in terms of zone of inhibition, minimum inhibitory concentration, minimum bactericidal concentration and minimum fungicidal concentration in camparison to the standard drugs. The results revealed that all synthesized compounds had shown potent to mild biological activity. Among the synthesized derivatives, (E)-N'-(3,4-dimethoxybenzylidene)isonicotinohydrazide 2e, (E)-N'-(3,4,5-trimethoxybenzylidene)isonicotinohydrazide 2f and (E)-N'-(4-hydroxy-3-methoxybenzylidene)isonicotinohydrazide 2g were found to be the most effective antimicrobial compounds, whereas compounds 2g and 2k were the most potent antioxidants with significant hydrogen peroxide scavenging activity.

Synthesis and characterization of (Z)-N-(1-[2-{3-[(dimethylamino)methyl)]-2-methoxyphenyl}-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl]ethylidene) benzenamine derivatives as potent antifungal agents.

In the present study, a series of (Z)-N-(1-[2-{3-[(dimethylamino)methyl)]-2-methoxyphenyl}-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl]ethylidene)benzenamine derivatives have been synthesized and characterized by IR, 1H NMR and 13C NMR spectra. All the synthesized compounds were evaluated for their antifungal activity and were compared with the standard drug, clotrimazole. The compounds demonstrated excellent to weak antifungal activity. Among the synthesized derivatives, 4f and 4h showed significant activity and 4c exhibited moderate activity against Candida albicans, Candida tropicalis and Aspergillus niger as compared with the standard antifungal agent - clotrimazole. The minimum inhibitory concentration of the compounds was in the range of 1.62-25 microg/mL against fungi. Furthermore, the substitution of chloro, nitro and methoxy groups at para position of benzene moiety play an important role in enhancing the antifungal activity of this class of compounds.

Synthesis, characterization and evaluation of mannich bases as potent antifungal and hydrogen peroxide scavenging agents.

In the present study, (E)-2-{ [-2-(2,4-Dinitrophenyl)hydrazono]methyl} phenol (3) was synthesized and used as key intermediate for the synthesis of new Mannich bases. All the synthesized compounds were evaluated for their antifungal activity against three fungal strains Candida albicans, Candida tropicalis and Aspergillus niger and antioxidant activity. The structure of these compounds was confirmed by IR, 1H NMR and 13C NMR studies. Most of the compounds exhibited moderate to significant activities.

Synthesis, characterization and evaluation of benzylidene analogues as a new class of potential antioxidant agents.

Seventeen analogues of benzylidene were synthesized and evaluated for in vitro hydrogen peroxide scavenging activity. The structure of the newly synthesized compounds were confirmed by elemental and spectral (IR, 1H-NMR, 13C-NMR) studies. The antioxidant activity of the titled compounds was evaluated. Compounds: 4h--N'-[2-amino-3-(morpholinomethyl)benzylidene]isonicotinohydrazide, 4p 7-(4-(2-amino-3-[(2-isonicotinoylhydrazono)methyl]benzyl}piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquino- line-3-carboxylic acid and 4q 7-(4-{2-amino-3-[(2 isonicotinoylhydrazono)methyl]benzyl} piperazin-1-yl)-1-ethyl-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid were the most active compounds with significant hydrogen peroxide scavenging activity.

Herbal products as skincare therapeutic agents against ultraviolet radiation-induced skin disorders.

This paper aims to highlight the pharmacological aspects of listed herbal skincare products used for the treatment of various disorders caused due to ultraviolet radiation. The pharmacological aspects include safety and efficacy validation as per regulatory guidelines following internationally accepted scientific principles for their development of skincare products. Herbal products have always been used traditionally for the treatment of various skin ailments and have become more prevalent because of their safety and high efficacy benefits. The incorporation of synthetic molecules and chemical substances in the different medicinal and pharmaceutical formulations is the leading cause of the dermal toxicity. Therefore, the developments of herbal skincare products containing scientifically validated herbal ingredients have better acceptance, respect, and belief in the society. The listed herbal products in this review can help take forward the commercial development of skincare products for therapeutic as well as beauty care purposes from such plants.

Quinoxaline: A Chemical Moiety with Spectrum of Interesting Biological Activities.

Quinoxaline (C8H6N2), commonly called 1,4-diazanaphthalene, 1,4-benzodiazine, or benzopyrazine, is a very potent nitrogenous heterocyclic moiety consisting of a benzene ring fused with the pyrazine ring. A number of different methods for the synthesis of quinoxaline derivatives have been reported in the literature, but the most effective method, commonly used for the synthesis of quinoxaline analogues involves the condensation of substituted o-phenylenediamines with 1, 2- dicarbonyl compounds in the presence of different catalyst(s). The presence of different types of catalysts and their concentration affects the overall yield of the product. Quinoxaline not only plays an important role as an organic reaction intermediate but also has a wide spectrum of interesting biological activities viz. antibacterial, antifungal, anticancer, anti-inflammatory, antiviral, and antiprotozoal activity, etc. Some commercially available drug molecules containing quinoxaline moiety are echinomycin (as antibacterial, antineoplastic, and nucleic acid inhibitor), triostins (cyclic desipeptide as an antibacterial agent), dioxidine and mequindox (as antibacterial agents), carbadox (controlling swine dysentery), desoxycarbadox (as swine growth promoter) and panadipion (as hepatoprotective agent), etc. A large number of quinoxaline analogues possessing different biological activities and their synthetic procedures have been patented worldwide.

Synthesis and anti-inflammatory activity of some novel biphenyl-4-carboxylic acid 5-(arylidene)-2-(aryl)-4-oxothiazolidin-3-yl amides.

Some new biphenyl-4-carboxylic acid 5-(arylidene)-2-(aryl)-4-oxothiazolidin-3-yl amides have been synthesized and evaluated for anti-inflammatory activity. Biphenyl-4-carboxylic acid hydrazide was converted to the corresponding aryl hydrazones using aryl aldehydes in the presence of catalytic amount of glacial acetic acid. The aryl hydrazones on reaction with thioglycolic acid in the presence of anhydrous zinc chloride yielded the biphenyl-4-carboxylic acid 2-(aryl)-4-oxothiazolidin-3-yl amides, which again on reaction with aromatic aldehydes in the presence of anhydrous sodium acetate and glacial acetic acid furnished the title compounds. The structures of all these newly synthesized compounds were confirmed by their analytical and spectral data which were in full agreement with proposed structures. All compounds were screened for anti-inflammatory activity employing carrageenan test at the dose of 10 mg/kg and exhibited significant activities.

Design and biological evaluation of biphenyl-4-carboxylic acid hydrazide-hydrazone for antimicrobial activity.

Seven biphenyl-4-carboxylic acid hydrazide-hydrazones have been synthesized. These hydrazone derivatives were characterized by CHN analysis, IR, and 1H NMR spectral data. All the compounds were evaluated for their in vitro antimicrobial activity against two Gram negative strains (Escherichia coli and Pseudomonas aeruginosa) and two Gram positive strains (Bacillus subtilis and Staphylococcus aureus) and fungal strain Candida albicans and Aspergillus niger All newly synthesized compounds exhibited promising results.

Development and characterization of nanoparticles of glibenclamide by solvent displacement method.

The aim of this study was to formulate nanoparticles (NPs) containing glibenclamide (GB) prepared with Eudragit L100 to achieve a better release profile suitable for per oral administration with enhanced efficacy. The NPs were prepared by solvent displacement method. The influence of various formulation factors (drug : polymer ratio and concentration of surfactants) on particle size, size distribution, zeta potential, drug loading and encapsulation efficiency were investigated. Drug : polymer ratio was observed to be important parameter influencing mean particle size, beside others. Encapsulation efficiency and drug loading capacity were found to be increased as drug concentration increases with respect to polymer. Addition of surfactants showed a promising result in decreasing particle size of NPs. Dissolution study revealed increased release of GB from NPs. Transmission electron microscopy (TEM) study revealed spherical morphology of the developed NPs. Differential scanning calorimetry (DSC) studies confirmed phase transition behavior of NPs. They also showed very significant change in saturation solubility in comparison with pure drug. Developed NPs revealed a decreased t(min) and enhanced bioavailability and hence superior activity as compared to plain GB in alloxan-induced diabetic rabbit model. The developed NPs could reduce dose frequency, decrease side effects, and improve patient compliance.

Hypolipidemic effect of ethanolic extract from the leaves of Hibiscus sabdariffa L. in hyperlipidemic rats.

The present study is designed to investigate the hypolipidemic effect of ethanolic extract from the leaves of Hibiscus sabdariffa L. (HSEE) in hyperlipidemic rats. In the present work, HSEE was evaluated at three doses (i.e. 100, 200 and 300 mg/kg, orally) in cholesterol-induced (2 g/kg, orally) hyperlipidemic Wistar rats. Atorvastatin (10 mg/kg, orally) was used as the standard drug. Administration of HSEE (200 mg/kg and 300 mg/kg) together with continuous cholesterol feeding for four weeks showed significant reduction in serum cholesterol level by 18.5% and 22%, respectively (p < 0.05); serum triglyceride level by 15.6% and 20.6%, respectively (p < 0.05); serum LDL level by 24% and 30%, respectively (p < 0.05), and serum VLDL level by 15.5% and 20.5%, respectively (p < 0.05), as compared to cholesterol group. However, no significant change in HDL level was observed. HSEE 300 mg/kg was more effective than HSEE 200 mg/kg dose but less effective than the standard drug, atorvastatin. HSEE 100 mg/kg did not show any significant reduction in lipid levels. These results indicate that HSEE exhibit the hypolipidemic effect and among all HSEE groups investigated, HSEE 300 mg/kg has the best hypolipidemic effect.