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Background: Thiadiazines are heterocyclic compounds that contain two nitrogen atoms and one sulfur atom in their structure. These synthetic molecules have several relevant pharmacological activities, such as antifungal, antibacterial, and antiparasitic. Objectives: The present study aimed to evaluate the possible in vitro and in silico interactions of compounds derived from thiadiazines. Methods: The compounds were initially synthesized, purified, and confirmed through HPLC methodology. Multi‐drug resistant bacterial strains of Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 were used to evaluate the direct and modifying antibiotic activity of thiadiazine derivatives. ADMET assays (absorption, distribution, metabolism, excretion, and toxicity) were conducted, which evaluated the influence of the compounds against thousands of macromolecules considered as bioactive targets. Results: There were modifications in the chemical synthesis in carbon 4 or 3 in one of the aromatic rings of the structure where different ions were added, ensuring a variability of products. It was possible to observe results that indicate the possibility of these compounds acting through the cyclooxygenase 2 mechanism, which, in addition to being involved in inflammatory responses, also acts by helping sodium reabsorption. The amine group present in thiadiazine analogs confers hydrophilic characteristics to the substances, but this primary characteristic has been altered due to alterations and insertions of other ligands. The characteristics of the analogs generally allow easy intestinal absorption, reduce possible hepatic toxic effects, and enable possible neurological and anti‐inflammatory action. The antibacterial activity tests showed a slight direct action, mainly of the IJ23 analog. Some compounds were able to modify the action of the antibiotics gentamicin and norfloxacin against multi‐drug resistant strains, indicating a possible synergistic action. Conclusions: Among all the results obtained in the study, the relevance of thiadiazine analogs as possible coadjuvant drugs in the antibacterial, anti‐inflammatory, and neurological action with low toxicity is clear. Need for further studies to verify these effects in living organisms is not ruled out. [ABSTRACT FROM AUTHOR]

New fluorinated 1,2,4-triazin-4-ones 2–24 have been prepared using straightforward approaches. The reaction of 4-amino-3-mercapto-6-(trifluoromethyl)-1,2,4-triazin-5(4H)-one (2) with aromatic aldehydes produced 4-((4-substitutedbenzylidene)amino)-3-mercapto-6-(trifluoromethyl)-1,2,4-triazin-5(4H)-ones (5–9), which were cyclized by thioglycolic acid to give 2-(4-subsitiutedphenyl)-3-(3-mercapto-5-oxo-6-(trifluoromethyl)-1,2,4-triazin-4(5H)-yl)thiazolidin-4-ones (10–14). 7-Methyl-3-(trifluoromethyl)-4H-[1, 3, 4]thiadiazolo[2,3-c][1, 2, 4]triazin-4-one (4) was synthesized by the condensation of 2 with acetaldehyde or by reaction with cyano compounds, followed by self-cyclization in dry benzene. Cyclization of compound 2 by reaction with aromatic acids yielded 7-substitutedphenyl-3-(trifluoromethyl)-4H-[1, 3, 4]thiadiazolo[2,3-c][1, 2, 4]triazin-4-ones (15–19). Reaction of compound 2 with cyanamide produced 1-(4-oxo-3-(trifluoromethyl)-4H-[1, 3, 4]thiadiazolo[2,3-c][1, 2, 4]triazin-7-yl)guanidine (20). Alkylation of compound 2 with phenacyl bromide produced 4-amino-3-((2-oxo-2-phenylethyl)thio)-6-(trifluoromethyl)-1,2,4-triazin-5(4H)-one (21) which upon heating in the same media furnished 7-phenyl-3-(trifluoromethyl)-4H,8H-[1, 2, 4]triazino[3,4-b][1, 3, 4]thiadiazin-4-one (22). The reaction of Schiff′s bases 5 or 6 with phenacyl bromide gave 8-benzoyl-7-(4-halophenyl)-3-(trifluoromethyl)-4H,8H-[1, 2, 4]triazino[3,4-b][1, 3, 4]thiadiazin-4-ones (23–24). All of the newly synthesized compounds were characterized by spectral measurements and elemental analysis. The biological evaluation was also described. All compounds were screened for antibacterial, antifungal, and anti-biofilm activities. The findings confirm that the fluorinated 1,2,4-triazin-4-ones appear to be promising compounds as antibacterial, antifungal, and anti-biofilm agents. [ABSTRACT FROM AUTHOR]

Based on the pharmaceutical importance of the coumarin scaffold, we decided here to synthesize and evaluate the biological activity of some new coumarins. The new coumarin derivatives were synthesized starting from 3-(2-bromoacetyl)-2H-chromen-2-one (1) and their structures were clarified by fully spectral data. Ten of the new synthesized compounds were investigated for their anticancer activity against 60 human cancer cell lines by NCI USA. All the tested compounds showed good to mild activity against the tested cancer cell lines. Compounds 5, 7, and 8 were the most active against Renal Cancer UO-31 cancer cell line with growth inhibition percentage of 38.74%, 45.09%, and 34.65%, respectively. Where, compound 12 demonstrated strong to moderate activity toward Leukemia K-562, Renal Cancer UO-31and Breast Cancer T-47D cancer cell lines with growth inhibition percentage of 27.00%, 31.59%, and 32.98%, respectively. [ABSTRACT FROM AUTHOR]

In this article, we applied ultrasonic irradiation as an ecofriendly, green, efficient approach for the synthesis of a new 1,3-thiazoles and 1,3,4-thiadiazines under solvent-free conditions. Thus, thiocarbohydrazide condenses with N-(thiazol-2-yl)acetamide (2) in different molar ratios under ultrasonic irradiation afforded mono and bis thiocarbohydrazons 3a,b, respectively. Thiocarbohydrazones were reacted with α-haloketone, α-haloester as well as hydrazonoyl halides under ultrasonic conditions afforded 1,3-thiazole 4, 1,3-thiazolinone 5 and 1,3,4-thiadiazines 6 and 11a–c, respectively. The reaction of monohydrazone 3a with phthalic anhydride derivatives afforded phthalazines 7a,b in a good yield. Ultrasonic irradiation has benefits such as greater purity, lower cost, high yields, and simple workups compared to the conventional methods. All the new compounds were screened for antimicrobial activity against different tested microbes. Most of the newly synthesized compounds exhibited potent to moderate activities toward the tested microbes. Compounds that exhibited potent antimicrobial activities were selected to measure their MIC and MBC values. The results revealed that compounds 3a, 3b, 8, 10, and 11a showed lower MIC against Staphylococcus aureus with the values of 39.06, 78.13, 9.77, 39.06 and 39.06 µg/ml, respectively. Meanwhile, the MBC values were found to be acceptable for 3a and 10 of 156 and 312, respectively.

PurposeThe oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) promotes gene transcription involved in cancer, and its activation by IL-6 is found in head and neck squamous cell carcinoma. Four triazolothiadizine STAT3 pathway inhibitors were evaluated to prioritize a single compound for in vivo examination.MethodsMetabolic stability in mouse liver microsome incubation was used to evaluate four triazolothiadizine analogues, and UPCDC-10205 was administered to mice IV as single or multiple doses to evaluate toxicity. Single-dose pharmacokinetics (PK), bioavailability and metabolism were studied after IV 4 mg/kg, PO 4 mg/kg, or PO 30 mg/kg suspension in 1% carboxymethyl cellulose. Mice were euthanized between 5 min to 24 h after dosing, and plasma and tissues were analyzed by LC-MS. Non-compartmental PK parameters were determined.ResultsOf the four triazolothiadizine analogues evaluated, UPCDC-10205 was metabolically most stable. The maximum soluble dose of 4 mg/kg in 10% Solutol™ was not toxic to mice after single and multiple doses. PK analysis showed extensive tissue distribution and rapid plasma clearance. Bioavailability was ~5%. A direct glucuronide conjugate was identified as the major metabolite which was recapitulated in vitro.ConclusionsRapid clearance of UPCDC-10205 was thought to be the result of phase II metabolism despite its favorable stability in a phase I in vitro metabolic stability assay. The direct glucuronidation explains why microsomal stability (reflective of phase I metabolism) did not translate to in vivo metabolic stability. UPCDC-10205 did not demonstrate appropriate exposure to support efficacy studies in the current formulation.

Structure-activity relationship studies of a 1,2,4-triazolo-[3,4-b]thiadiazine scaffold, identified in an HTS campaign for selective STAT3 pathway inhibitors, determined that a pyrazole group and specific aryl substitution on the thiadiazine were necessary for activity. Improvements in potency and metabolic stability were accomplished by the introduction of an α-methyl group on the thiadiazine. Optimized compounds exhibited anti-proliferative activity, reduction of phosphorylated STAT3 levels and effects on STAT3 target genes. These compounds represent a starting point for further drug discovery efforts targeting the STAT3 pathway.

In this article, we applied ultrasonic irradiation as an ecofriendly, green, efficient approach for the synthesis of a new 1,3-thiazoles and 1,3,4-thiadiazines under solvent-free conditions. Thus, thiocarbohydrazide condenses with N-(thiazol-2-yl)acetamide (2) in different molar ratios under ultrasonic irradiation afforded mono and bis thiocarbohydrazons 3a,b, respectively. Thiocarbohydrazones were reacted with α-haloketone, α-haloester as well as hydrazonoyl halides under ultrasonic conditions afforded 1,3-thiazole 4, 1,3-thiazolinone 5 and 1,3,4-thiadiazines 6 and 11a–c, respectively. The reaction of monohydrazone 3a with phthalic anhydride derivatives afforded phthalazines 7a,b in a good yield. Ultrasonic irradiation has benefits such as greater purity, lower cost, high yields, and simple workups compared to the conventional methods. All the new compounds were screened for antimicrobial activity against different tested microbes. Most of the newly synthesized compounds exhibited potent to moderate activities toward the tested microbes. Compounds that exhibited potent antimicrobial activities were selected to measure their MIC and MBC values. The results revealed that compounds 3a, 3b, 8, 10, and 11a showed lower MIC against Staphylococcus aureus with the values of 39.06, 78.13, 9.77, 39.06 and 39.06 µg/ml, respectively. Meanwhile, the MBC values were found to be acceptable for 3a and 10 of 156 and 312, respectively. [ABSTRACT FROM AUTHOR]

Background: Children with chronic IF require long-term home parenteral nutrition (HPN), administered through a central venous catheter. Catheter-related bloodstream infection (CRBSI) with Staphylococcus aureus is known to be a serious infection with a high mortality rate and risk of complications. A standardized protocol on the management of S aureus CRBSIs in children receiving HPN is lacking. The aim of this study is to evaluate the effectiveness and safety of the current management in an HPN expertise center in the Netherlands., Methods: We performed a retrospective descriptive cohort study between 2013 and 2022 on children 0-18 years of age with chronic IF requiring long-term HPN. Our primary outcomes were the incidence of S aureus CRBSI per 1000 catheter days, catheter salvage attempt rate, and successful catheter salvage rate. Our secondary outcomes included complications and mortality., Results: A total of 74 patients (39 male; 53%) were included, covering 327.8 catheter years. Twenty-eight patients (38%) had a total of 52 S aureus CRBSIs, with an incidence rate of 0.4 per 1000 catheter days. The catheter salvage attempt rate was 44% (23/52). The successful catheter salvage rate was 100%. No relapse occurred, and no removal was needed after catheter salvage. All complications that occurred were already present at admission before the decision to remove the catheter or not. No patients died because of an S aureus CRBSI., Conclusion: Catheter salvage in S aureus CRBSIs in children receiving HPN can be attempted after careful consideration by a multidisciplinary team in an HPN expertise center., (© 2024 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Reduced-risk insecticides and mirid predators have been used to control Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) in tomato crops. However, even when causing low mortality to the beneficial insects, these products might cause side effects. This study investigated the sublethal and transgenerational effects of buprofezin, cyantraniliprole, and spiromesifen on Macrolophus basicornis (Stal) (Hemiptera: Miridae). After 72 h of exposure of third-instar nymphs and adults to residues on tomato leaves, adult couples were formed and kept in cages with residue-free tomato leaves. The leaves were changed every 48 h and the offspring were assessed in 6 different periods. Body size was assessed by measuring the hind-tibia length of adults (F 0 ) from exposed nymphs and in three different offspring groups. None of the insecticide residues caused a reduction on offspring populations or affected the body size of adults in generation F 0 . Regardless, buprofezin and spiromesifen reduced the tibia length of adults (F 1 ) from exposed nymphs assayed in the third mating period. Cyantraniliprole did not affect any parameter and could be recommended for control of B. tabaci in association with M. basicornis releases. This study may contribute to future field assays of the compatibility of these insecticides with M. basicornis., (© 2024. Sociedade Entomológica do Brasil.)

Early developmental exposure to environmental toxicants may play a role in the risk for developing autism. A variety of pesticides have direct effects on retinoic acid (RA) signaling and as RA signaling has important roles in neurodevelopment, such compounds may cause developmental neurotoxicity through an overlapping adverse outcome pathway. It is hypothesized that a pesticide's embryonic effects on retinoid function may correspond with neurobehavioral disruption later in development. In the current studies, we determined the effects of RA-acting pesticides on neurobehavioral development in zebrafish. Buprofezin and imazalil caused generalized hypoactivity in the larval motility test, whereas chlorothalonil and endosulfan I led to selective hypoactivity and hyperactivity, respectively. With buprofezin, chlorothalonil, and imazalil, hypoactivity and/or novel anxiety-like behaviors persisted in adulthood and buprofezin additionally decreased social attraction responses in adulthood. Endosulfan I did not produce significant adult behavioral effects. Using qPCR analyses of adult brain tissue, we observed treatment-induced alterations in RA synthesis or catabolic genes, indicating persistent changes in RA homeostasis. These changes were compound-specific, with respect to expression directionality, and potential patterns of homeostatic disruption. Results suggest the likely persistence of disruptions in RA signaling well into adulthood and may represent compensatory mechanisms following early life stage exposures. This study demonstrates that early developmental exposure to environmental toxicants that interfere with RA signaling causes short as well as long-term behavioral disruption in a well-established zebrafish behavioral model and expand upon the meaning of the RA adverse outcome pathway, indicating that observed effects likely correspond with the nature of underlying homeostatic effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dazomet is a dry powder formulation that releases toxic gas containing methyl isothiocyanate, which controls soil-borne pests and weeds, improving crop yields when applied to moist soils. To explore the efficacy of dazomet fumigation in the cultivation of the perennial herb Codonopsis pilosula, four typical cultivars (G1, G2, W1 and TCK) in Gansu Province were selected for seedling cultivation after soil fumigation (F) by dazomet, and non-fumigated soil was used as a control (CK). The experiments took 2 years to complete. The functional diversity of the soil enzymes and microorganisms, seedling emergence and physiological characteristics, and the quality and yield of Codonopsis seedlings and Radix were assessed. The results showed that the seed emergence rate, seedling re-green rate and several antioxidant enzymatic activities improved in the treatments involving soil fumigation with dazomet, and membrane lipid peroxidation in the seedlings decreased. On average, compared with those of the respective controls, the root viability and yield of the seedlings of the tested cultivars also increased by 34.87% and 42.4%, respectively, and the incidence of root rot in the seedlings was reduced by 83.9%, compared with their respective controls. After harvest, the yield increased by 23.9%, the incidence of root rot decreased by 61.3%, increase in yield and a 61.3% reduction in incidence, and the medicinal materials were determined to be safe and residue-free. The effects of fumigation were cultivar-specific and were especially prominent in G2. Therefore, soil fumigation with dazomet could improve the quality and productivity of Codonopsis pilosula seedlings. Taken together, these findings suggest that when herbs are bred by seedling transplantation, especially cultivars of good quality but poor resistance or species with rare germplasm resources, soil fumigation provides a way to improve cultivation effectiveness and, more importantly, ensures the probability of successfully breeding the species., (© 2024. The Author(s).)

Background: Catheter-related bloodstream infections (CRBSIs) in patients receiving home parenteral nutrition (HPN) for chronic intestinal failure (CIF) are associated with significant morbidity and financial costs. Taurolidine is associated with a reduction in bloodstream infections, with limited information on the cost-effectiveness as the primary prevention. This study aimed to determine the cost-effectiveness of using taurolidine-citrate for the primary prevention of CRBSIs within a quaternary hospital., Methods: All patients with CIF receiving HPN were identified between January 2015 and November 2022. Data were retrospectively collected regarding patient demographics, HPN use, CRBSI diagnosis, and use of taurolidine-citrate. The direct costs associated with CRBSI-associated admissions and taurolidine-citrate use were obtained from the coding department using a bottom-up approach. An incremental cost-effective analysis was performed, with a time horizon of 4 years, to compare the costs associated with primary and secondary prevention against the outcome of cost per infection avoided., Results: Forty-four patients received HPN within this period. The CRBSI rates were 3.25 infections per 1000 catheter days before the use of taurolidine-citrate and 0.35 infections per 1000 catheter days after taurolidine-citrate use. The incremental cost-effectiveness ratio indicates primary prevention is the weakly dominant intervention, with the base case value of $27.04 per CRBSI avoided. This held with one-way sensitivity analysis., Conclusion: Taurolidine-citrate in the primary prevention of CRBSIs in patients with CIF receiving HPN is associated with reduced hospital costs and infection rates., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Spiders, the major predatory enemies of insect pests in fields, are vulnerable to insecticides. In this study, we observed that the recommended dose of buprofezin delayed the molting of the pond wolf spider Pardosa pseudoannulata, although it had no lethal effect on the spiders. Since buprofezin is an insect chitin biosynthesis inhibitor, we identified two chitin synthase genes (PpCHS1 and PpCHS2) in P. pseudoannulata. Tissue-specific expression profiling showed that PpCHS1 was most highly expressed in cuticle. In contrast, PpCHS2 showed highest mRNA levels in the midgut and fat body. RNAi knockdown of PpCHS1 significantly delayed the molting of 12-days old spiderlings, whereas no significant effect on the molting was observed in the PpCHS2-silencing spiderlings. The expression of PpCHS1 was significantly suppressed in the spiderlings treated with buprofezin, but rescued by exogenous ecdysteroid ponasterone A (PA). Consistent with this result, the molting delay caused by buprofezin was also rescued by PA. The results revealed that buprofezin delayed the molting of spiders by suppressing PpCHS1 expression, which will benefit the protection of P. pseudoannulate and related spider species., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Taurolidine lock, a technique used to prevent or treat catheter-related bloodstream infection (CRBSI), is effective in adult and paediatric patients but has been described rarely in neonates. The aim of this descriptive retrospective study, was to determine the feasibility and direct outcomes of prophylactic and therapeutic taurolidine locks in term and preterm neonates., Methods: We implemented the use of therapeutic taurolidine lock in addition to antibiotic treatment with the aim of catheter salvage in critical neonates with difficult vascular access (group 1). In addition, we introduced taurolidine lock as a preventive measure in neonates with a central venous catheter (CVC) at high risk of developing CRBSI (group 2). Every 24 h (in the treatment group) a 2% taurolidine solution was injected and the catheter locked for at least 120 min, until infection clearance (group 1). In the preventive group, the catheter was locked for 30 min every 48 h until CVC removal (group 2)., Findings: Thirty-seven neonates who received taurolidine were included in this study. We did not observe any major adverse events. In group 1 (21 cases), clinical symptom disappearance and bacteraemia clearance were achieved without catheter removal in 18 cases (85.7%); in the other three neonates the catheter was removed shortly after the start of the locks as it was possible to replace the CVC. In group 2 (16 neonates), no CRBSI was observed during the duration of the catheter placement., Conclusions: In this retrospective study, taurolidine was successfully used in neonates both for prevention and treatment of CRBSI, without major undesired effects. A larger cohort and a randomized clinical trial is warranted in order to establish its efficacy and safety in neonates., (Copyright © 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Quantitative structure-activity relationship (QSAR) analysis has been performed in order to predict the antifungal activity of dihydroindeno and indeno thiadiazines against toxigenic fungus Aspergillus flavus. The studied compounds were classified according to their lipophilicity using the principal component analysis (PCA). The partial least square regression (PLSR) was used to distinguish the most important molecular descriptors for non-linear modeling. Artificial neural networks (ANNs) were applied for the antifungal activity prediction. The best QSAR models were validated by statistical parameters and graphical methods. High agreement between the observed and predicted antifungal activity values indicated the good quality of the derived QSAR models. The obtained QSAR-ANN models can be used to predict the antifungal activity of dihydroindeno and indeno thiadiazines and of structurally similar compounds. The modeling of the antifungal activity can contribute to the synthesis of new antifungal agents with better ability to protect food and feed from the mycotoxins.

In our work, several 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-phenylhydrazone derivatives as α-glucosidase inhibitors (α-GIs) were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS spectrum. Then, their bio-activity against the α-glucosidase (α-Glu) was further evaluated. Among them, almost all compounds displayed better bio-activity with IC 50 from 31.23 ± 0.89 to 213.50 ± 4.19 μM than acarbose (IC 50  = 700.20 ± 10.55 μM). In particular, compound 5o showed the best potency to inhibit α-Glu in a mixed manner. Moreover, the action mechanisms of 5o were further clarified including fluorescence quenching, circular dichroism spectra, three-dimensional fluorescence spectra, molecular docking, etc. All mechanism studies revealed that 5o could arouse the changed secondary structure of α-Glu to hinder enzyme catalytic activity. It was observed from an in vivo study that 5o of 20 mg/kg could significantly decrease by 24.45 % postprandial blood glucose in mice vs. the control. Meanwhile, 5o had low drug-drug interaction potential and was likely to be an orally active compound. Moreover, 5o was observed to be no obvious cytotoxicity to HEK-293 cells. In summary, compound 5o exhibited one potential to be further applied as an antidiabetic drug., Competing Interests: Declaration of competing interest The authors confirm that this articles' content has no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

A series of new thiadiazine derivatives including 2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) propanoic acids (a) and 4-methyl-2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) pentanoic acids (b) were synthesized by reacting primary alkyl/aryl amines with CS 2 , followed by reaction with formaldehyde and amino acids. The chemical structures of synthesized compounds were confirmed by 13 C- NMR and 1 H- NMR techniques. The inhibitory potential of major inflammatory enzymes, COX-2 and 5-LOX was examined. Moreover, anti-nociceptive and anti-inflammatory activities were evaluated in the in vivo thermally induced nociceptive, and carrageenan induced paw edema models in mice. The in-vitro results reflect that these compounds exhibited concentration dependent inhibition of COX-2 and 5-LOX. The tested compounds at 50 mg/kg showed significant effect on thermally induced pain, and reduced latency time (seconds) as compared to the vehicle treated animals. Moreover, tested compounds exhibited percent inhibition of paw edema in the carrageenan induced paw edema model in mice. Furthermore, the binding modes of the most active COX-2 and 5-LOX inhibitors were determined through computational methods. The computational study reflects that the docked compounds have high binding affinities for COX-2 and 5-LOX enzymes, which leads to inhibition of these enzymes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The present paper cites literature data on methods of synthesis of α-thiocyanatocarbonyl compounds and methods of synthesis new bi-and multifunctional electrophilic reagents asmain and perspective building blocks for the construction of new heterocyclic systems.Also cited are data on systematic studies of synthesized polycentric electrophilic substrates in the reactions with various nucleophilic reagents of anionic and neutral nature leading to the construction of heterocyclic and macromolecular structures. [ABSTRACT FROM AUTHOR]

A series of 5-cyano-2-thiouracil derivatives, containing diverse hydrophobic groups in the 2-, 4- and 6-positions, were synthesized through one pot reaction of thiophene 2-carboxaldehyde, ethylcyanoacetate and thiourea using classic reflux-based method as well as microwave-assisted methods. Such prepared compounds were reacted with different electrophilic reagents to synthesize potent anti-microbial agents, e.g. 1,3,4-thiadiazinopyrimidine, hydrazide and triazolopyrimidine derivatives (compounds 4 a-e, 9 and 10 – 12 ) respectively. The density functional theory (DFT) was then applied to explore the structural and electronic characteristics of these materials. It is found that compound 12 exhibited the highest antibacterial and antifungal activity against C. Albicans showing six-fold increasing biological affinity compared to that of Colitrimazole drug with MIC values 7.8 and 49 μg/mL, respectively. All the synthesized compounds have been characterized based on their elemental analyses and spectral data. Such compounds can be submitted to in vivo antimicrobial studies in future works. [ABSTRACT FROM AUTHOR]

A series of Ethyl 2-[2-(2,5-disubstituted-1H-indol-3-yl)-4-oxothiazolid-3-ylamino]-5,6-dihydro-5-oxo-4H-1,3,4-thiadiazine-6-carboxylates (4a–g) were synthesized from cyclocondensation of Ethyl 2-{(2E)-2-[(2,5-disubstituted-1H-indol-3-yl) methy leno] hydrazine}-5-oxo-5,6-dihydro-4H-1,3,4-thiadiazine-6-carboxylates (3a–g) with thioglycolic acid in the presence of the catalytic amount of zinc chloride. The compounds 3a–g were obtained from the reaction of Ethyl 2-hydrazinyl-5,6-dihydro-5-oxo-4H-1,3,4-thiadiazine-6-carboxylate (2) with various substituted indole-3-carboxaldehydes 1a–g. Newly synthesized compounds were characterized by using IR, 1H NMR, Mass spectral and analytical data. Title compounds were evaluated for their in vitro antimicrobial activities against various microbial strains and selected compounds were tested for their analgesic and anti-inflammatory activities. Some of the newly synthesized Indolyl 4-thiazolidinone analogues displayed significant activity towards antimicrobial, analgesic and anti-inflammatory activities.

Synthesis of [3,4-b][1,3,4]thiadiazines from the condensation of 4-amino-6-methyl-3-thioxo-1,2,4-triazine-5(2H)-one (AMTTO) or 4-amino-1,4-dihydro-5-methyle-1,2,4-triazole-5-thione (AMTT) with phenacyl bromide in the presence of a catalytic amount of various heteropolyacids (HPAs) under refluxing conditions is reported. DOI: http://dx.doi.org/10.4314/bcse.v28i1.8