Sinteza i farmakološka evaluacija 3-cikloheksil-2-supstituiranih hidrazino-3H-kinazolin-4-ona kao analgetika i antiinflamatorika

A series of novel 3-cyclohexyl-2-substituted hydrazino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 3-cyclohexyl-2-hydrazino quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material, 3-cyclohexyl-2-hydrazino quinazolin-4(3H)-one, was synthesized from cyclohexyl amine. Title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic behavior. The compound 3-cyclohexyl-2-(1-methylbutylidene-hydrazino)-3H-quinazolin-4-one (4c) emerged as the most active compound of the series and is moderately more potent in its analgesic and anti-inflammatory activities compared to the reference standard diclofenac sodium. Interestingly, test compounds showed only mild ulcerogenic potential when compared to acetylsalicylic acid.Reakcijom amino skupine 3-cikloheksil-2-hidrazino kinazolin-4(3H)-ona s različitim aldehidima i ketonima sintetizirani su novi 3-cikloheksil-2-supstituirani hidrazino-kinazolin-4(3H)-oni. Početni spoj 3-cikoheksil-2-hidrazino kinazolin-4(3H)-on pripravljen je iz cikloheksilamina. Sintetizirani spojevi testirani su na analgetsko i protuupalno djelovanje te ulcerogena svojstva. Spoj 3-cikloheksil-2-(1-metilbutiliden-hidrazino)-3H-kinazolin-4-on (4c) imao je najjače analgetsko i protuupalno djelovanje, nešto jače nego referentni spoj diklofenak natrij. Osim toga, testirani spojevi imaju samo blago ulcerogeno djelovanje u usporedbi s acetilsalicilnom kiselinom

Sinteza i farmakološko ispitivanje novih 4-(3-etilfenil)-1-supstituiranih 4H-[1,2,4]triazolo[4,3-a]kinazolin-5-ona kao nove klase H1-antihistaminika

A series of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones (4a-j) were synthesized by the cyclization of 3-(3-ethylphenyl)-2-hydrazino-3H-quinazolin-4-one (3) with various one-carbon donors. The starting material, compound 3, was synthesized from 3-ethyl aniline by a new innovative route with improved yield. When tested for their in vivo H1-antihistaminic activity on conscious guinea pigs, all test compounds protected the animals from histamine induced bronchospasm significantly. Compound 4-(3-ethylphenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (4b) emerged as the most active compound of the series and it is more potent (74.6 % protection) compared to the reference standard chlorpheniramine maleate (71 % protection). Compound 4b shows negligible sedation (10 %) compared to chlorpheniramine maleate (30 %). Therefore compound 4b can serve as the leading compound for further development of a new class of H1-antihistamines.Ciklizacijom 3-(3-etilfenil)-2-hidrazino-3H-kinazolin-4-ona (3) s različitim donorima jednog C atoma sintetizirana je serija novih 4-(3-etilfenil)-1-supstituiranih 4H-[1,2,4]triazolo[4,3-a]kinazolin-5-ona (4a-j). Početni spoj 3 pripravljen je iz 3-etil anilina na novi, inovativni način, s poboljšanim iskorištenjem. U testovima in vivo na zamorcima, svi testirani spojevi pokazali su značajno zaštitno djelovanje protiv bronhospazma induciranog histaminom. Spoj 4-(3-etilfenil)-1-metil-4H-[1,2,4]triazolo[4,3-a]kinazolin-5-on (4b) najaktivniji je među testiranim spojevima (zaštita 74.6 %) i jači od referentnog standarda klorfeniramin maleata (zaštita 71 %). Spoj 4b pokazuje zanemarivu sedaciju (10 %) u usporedbi s klorfeniramin maleatom (30 %). Stoga spoj 4b može biti vodeći spoj za daljnji razvoj nove klase H1-antihistaminika

Design, synthesis and H1-antihistaminic activity of novel 1-substituted-4-(3-chlorophenyl)-[1,2,4] triazolo [4,3-a] quinazolin-5(4H)-ones

In the present study a series of 1-substituted-4-(3-chlorophenyl)-[1,2,4] triazolo [4,3-a] quinazolin-5(4H)-ones were synthesized and screened for their H1-antihistaminic activity. The synthesized compounds were characterized by IR, 1H-NMR, mass spectral data and purity of the compounds was determined by elemental analysis. Antihistaminic activity of the title compounds was evaluated by histamine induced bronchoconstriction method in guinea pigs. Among the series, 4-(3-chlorophenyl)-1-methyl-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one (S5) was the most potent with the percentage protection of 69.65% and its potency is comparable to the reference drug chlorpheniramine maleate (70.09% protection). Interestingly the sedative property of compound S5 was found to be negligible (5.36%) when compared to chlorpheniramine maleate (34.92%)

Anticonvulsant activity of novel 1-(morpholinomethyl)-3-substituted isatin derivatives

A variety of novel isatin derivatives 5a–5j and 6a–6j were synthesized and characterized by spectroscopic means and elemental analysis. The title compounds were investigated for antiepileptic activity using MES and scPTZ seizures tests. Neurotoxicity study was performed by the rotorod test. The relationship between the functional group variation and the biological activity of the evaluated compounds was discussed. Among the synthesized analogs, the most active one was 6f that revealed protection in MES at a dose of 30 mg/kg (i.p.) after 0.5 h and 4 h. This molecule also provided protection in the scPTZ at a dose of 100 mg/kg (0.5 h) and 300 mg/kg (4 h)

THE PRELIMINARY PHYTOCHEMICAL ANALYSIS AND ORAL ACUTE TOXICITY STUDY OF STEM BARK OF SYZYGIUM CUMINI

Objective: The current subject field was carried out to evaluate phytochemical analysis and acute toxicity study of the stem bark of Syzygium cumini.Methods: The ethanol extraction was made by the Soxhlet extraction method. Phytochemical screening was performed by applying standard methods. The oral administration of the drug in treating a group is done by using a curved ball-tipped intubation needle affixed to a 3 ml syringe and animal's observed from cage side observations. All the animals were anesthetized with ether anesthesia; blood was collected from orbital puncture and analysis was made by standard methods. Several organs were collected by dissecting abdominal, thoracic and cranial cavities and each weighed by using a sensitive electronic balance. Fixation was made with 10% buffered formalin and processed for histological embedding by Carleton's histological techniques. Statistical data analyzed by statistical software Sigma Plot 10.Results: The phytochemical screening revealed the presence of flavonoids, tannins, carbohydrates, sterols and amino acids. The oral acute toxicity study showed no detectable clinical signs of toxicity and mortality during the study period of 14 d. There were no statistically significant alterations in body weights, organ weights, and hematological parameters compared to control group. The microscopic anatomy of the reproductive organs and liver showed normal architecture. Conclusion: The outcome of the study showed that the LD50 of the drug was greater than 5000 mg/kg body weight. The phytochemicals present in stem bark of Syzygium cumini can be employed in the fabrication of innovative medication for several diseases.Â

Synthesis, characterization and in vitro antimicrobial activity of some 1-(substitutedbenzylidene)-4-(4-(2-(methyl/phenyl)-4-oxoquinazolin-3(4H)-yl)phenyl)semicarbazide derivatives

A series of 1-(substitutedbenzylidene)-4-(4-(2-(methyl/phenyl)-4-oxoquinazolin-3(4H)-yl) phenyl)semicarbazide derivatives were synthesized with the aim of developing potential antimicrobials. It was characterized by FT-IR, 1H NMR, Mass spectroscopy and elemental analysis. In addition, the in vitro antibacterial and antifungal properties were tested against some human pathogenic microorganisms by employing the disc diffusion technique and agar streak dilution method. All title compounds showed activity against the entire strain of microorganisms. The relationship between the functional group variation and the biological activity of the evaluated compounds were well discussed. Based on the results obtained, compound 5j was found to be very active compared to the rest of the compounds which were subjected to antimicrobial assay

Synthesis and antimicrobial activities of 1-(3-benzyl-4-oxo-3H-quinazolin-2-yl)-4-(substituted)thiosemicarbazide derivatives

A series of 1-(3-benzyl-4-oxo-3H-quinazolin-2-yl)-4-(substituted) thiosemicarbazides (AS1-AS10) were obtained by the reaction of 2-hydrazino- 3-benzyl quinazolin-4(3H)-one (6) with different dithiocarbamic acid methyl ester derivatives. The key intermediate 3-benzyl-2-thioxo-2,3-dihydro-1Hquinazolin-4-one (4) was obtained by reacting benzyl amine (1) with carbon disulphide and sodium hydroxide in dimethyl sulphoxide to give sodium dithiocarbamate, which was methylated with dimethyl sulfate to yield the dithiocarbamic acid methyl ester (2) and condensed with methyl anthranilate (3) in ethanol yielded the desired compound (4) via the thiourea intermediate. The SH group of compound (4) was methylated for the favorable nucleophilic displacement reaction with hydrazine hydrate, which afford 2-hydrazino-3- benzyl-3H-quinazolin-4-one (6). The IR, 1H, and 13C NMR spectrum of these compounds showed the presence of peaks due to thiosemicarbazides, carbonyl (C=O), NH and aryl groups. The quinazolin-4-one moiety molecular ion peaks (m/z 144) were observed all the mass spectrum of compounds (AS1-AS10). Elemental (C, H, N) analysis satisfactorily confirmed purity of the synthesized compounds and elemental composition. All synthesized compounds were also screened for their antimicrobial activity against selective gram positive and gram negative by agar dilution method. In the present study compounds AS8 and AS9 were emerged as the most active compounds of the series

Recent Advances in Silver Nanoparticles Containing Nanofibers for Chronic Wound Management

Infections are the primary cause of death from burns and diabetic wounds. The clinical difficulty of treating wound infections with conventional antibiotics has progressively increased and reached a critical level, necessitating a paradigm change for enhanced chronic wound care. The most prevalent bacterium linked with these infections is Staphylococcus aureus, and the advent of community-associated methicillin-resistant Staphylococcus aureus has posed a substantial therapeutic challenge. Most existing wound dressings are ineffective and suffer from constraints such as insufficient antibacterial activity, toxicity, failure to supply enough moisture to the wound, and poor mechanical performance. Using ineffective wound dressings might prolong the healing process of a wound. To meet this requirement, nanoscale scaffolds with their desirable qualities, which include the potential to distribute bioactive agents, a large surface area, enhanced mechanical capabilities, the ability to imitate the extracellular matrix (ECM), and high porosity, have attracted considerable interest. The incorporation of nanoparticles into nanofiber scaffolds constitutes a novel approach to “nanoparticle dressing” that has acquired significant popularity for wound healing. Due to their remarkable antibacterial capabilities, silver nanoparticles are attractive materials for wound healing. This review focuses on the therapeutic applications of nanofiber wound dressings containing Ag-NPs and their potential to revolutionize wound healing

Emerging Trends in Curcumin Embedded Electrospun Nanofibers for Impaired Diabetic Wound Healing

Chronic wounds impose a significant burden on individuals and healthcare systems all over the world. Through clinical and preclinical investigations, inflammation and oxidative damage have been established as the primary causes of chronic wounds. These skin sores are easily exposed to microorganisms, which in turn cause inflammation and hinder the healing process. Additionally, microorganisms may cause an infection that prevents collagen production and reepithelialization. Curcumin’s antioxidant, anti-inflammatory, and anti-infectious characteristics, among others, have been identified as useful for diabetic wound healing management. However, curcumin has a few disadvantages, such as limited bioavailability, pH-dependent instability, water insolubility, slow cell absorption, and fast intracellular metabolism. These constraints necessitates the development of a suitable transporter to improve curcumin’s stability, bioavailability, therapeutic efficacy, and solubility. In recent years, Electrospun nanofiber mats have been an excellent choice for drug delivery because of their numerous advantages and inherent properties. Electrospun nanofibers have shown considerable promise as wound dressing materials. This review highlights the potential properties and recent advancements in using curcumin-loaded nanofibers for diabetic wound healing