Thiourea-functionalized aminoglutethimide derivatives as anti-leishmanial agents.

Aim: We aim to develop new anti-leishmanial agents against Leishmania major and Leishmania tropica. Materials & methods: A total of 23 thiourea derivatives of (±)-aminoglutethimide were synthesized and evaluated for in vitro activity against promastigotes of L. major and L. tropica. Results & conclusion: The N-benzoyl analogue 7p was found potent (IC50 = 12.7 µM) against L. major and non toxic to normal cells. The docking studies, indicates that these inhibitors may target folate and glycolytic pathways of the parasite. The N-hexyl compound 7v was found strongly active against both species, and lacked cytotoxicity against normal cells, whereas compound 7r, with a 3,5-bis-(tri-fluoro-methyl)phenyl unit, was active against Leishmania, but was cytotoxic in nature. Compound 7v was thus identified as a hit for further studies.

[Box: see text].

Frequency of vitamin D deficiency in children with iron deficiency anaemia and factors associated with vitamin D deficiency.

Objective: To evaluate vitamin D deficiency in children with iron-deficiency anaemia, and to identify the risk factors for such deficiency. METHODS: The cross-sectional study was conducted at the Children's Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from October 2021 to March 2022, and comprised children aged 1-5 years who had been diagnosed with iron-deficiency anaemia. Quantitative variables, like age, height, weight, gender, socioeconomic status and sibling status, were controlled by stratification. Data was compared to assess the risk factors of vitamin D deficiency among the subjects. Data was analysed using SPSS 22. RESULTS: Of the 236 children with iron-deficiency anaemia, 159(67.5%) also had vitamin D deficiency; 95(59%) girls and 65(41%) boys. Overall, 104(65.4%) subjects were aged 4-5 years and 55(34.6%) were aged 1-3 years. Vitamin D deficiency had significant association with female gender, older age, height and weight <5th centiles, educated parents, low to middle socioeconomic status, urban residence and higher number of siblings (p<0.05). CONCLUSIONS: The prevalence of vitamin D deficiency among children with iron-deficiency anaemia was found to be high.

Molecular Mechanisms of Ischemic Stroke: A Review Integrating Clinical Imaging and Therapeutic Perspectives.

Ischemic stroke poses a significant global health challenge, necessitating ongoing exploration of its pathophysiology and treatment strategies. This comprehensive review integrates various aspects of ischemic stroke research, emphasizing crucial mechanisms, therapeutic approaches, and the role of clinical imaging in disease management. It discusses the multifaceted role of Netrin-1, highlighting its potential in promoting neurovascular repair and mitigating post-stroke neurological decline. It also examines the impact of blood-brain barrier permeability on stroke outcomes and explores alternative therapeutic targets such as statins and sphingosine-1-phosphate signaling. Neurocardiology investigations underscore the contribution of cardiac factors to post-stroke mortality, emphasizing the importance of understanding the brain-heart axis for targeted interventions. Additionally, the review advocates for early reperfusion and neuroprotective agents to counter-time-dependent excitotoxicity and inflammation, aiming to preserve tissue viability. Advanced imaging techniques, including DWI, PI, and MR angiography, are discussed for their role in evaluating ischemic penumbra evolution and guiding therapeutic decisions. By integrating molecular insights with imaging modalities, this interdisciplinary approach enhances our understanding of ischemic stroke and offers promising avenues for future research and clinical interventions to improve patient outcomes.

A new acyl derivative of sulfadimethoxine inhibits phagocyte oxidative burst and ameliorates inflammation in a mice model of zymosan-induced generalised inflammation.

Chronic inflammation and oxidative stress play a pivotal role in the pathophysiology of most challenging illnesses, including cancer, Alzheimer's, cardiovascular and autoimmune diseases. The present study aimed to investigate the anti-inflammatory potential of a new sulfadimethoxine derivative N-(4-(N-(2,6-dimethoxypyrimidin-4-yl) sulfamoyl) phenyl) dodecanamide (MHH-II-32). The compound was characterised by applying 1H-, 13C-NMR, EI-MS and HRFAB-MS spectroscopic techniques. The compound inhibited zymosan-induced oxidative bursts from whole blood phagocytes and isolated polymorphonuclear cells with an IC50 value of (2.5 ± 0.4 and 3.4 ± 0.3 µg/mL), respectively. Furthermore, the inhibition of nitric oxide with an IC50 (3.6 ± 2.2 µg/mL) from lipopolysaccharide-induced J774.2 macrophages indicates its in vitro anti-inflammatory efficacy. The compound did not show toxicity towards normal fibroblast cells. The observational findings, gross anatomical analysis of visceral organs and serological tests revealed the non-toxicity of the compound at the highest tested intraperitoneal (IP) dose of 100 mg/kg in acute toxicological studies in Balb/c mice. The compound treatment (100 mg/kg) (SC) significantly (P < 0.001) downregulated the mRNA expression of inflammatory markers TNF-α, IL-1ß, IL-2, IL-13, and NF-κB, which were elevated in zymosan-induced generalised inflammation (IP) in Balb/c mice while upregulated the expression of anti-inflammatory cytokine IL-10, which was reduced in zymosan-treated mice. No suppressive effect was observed at the dose of 25 mg/kg. Ibuprofen was taken as a standard drug. The results revealed that the new acyl derivative of sulfadimethoxine has an immunomodulatory effect against generalised inflammatory response with non-toxicity both in vitro and in vivo, and has therapeutic potential for various chronic inflammatory illnesses.

Synthesis, density functional theory and kinetic studies of aminopyridine based α-glucosidase inhibitors.

Aims: The current study aimed to develop new thiourea derivatives as potential α-glucosidase inhibitors for the management of hyperglycemia in patients of Type 2 diabetes, with a focus on identifying safer and more effective antidiabetic agents. Materials & methods: New thiourea derivatives (1-16) were synthesized through single-step chemical transformation and evaluated for in vitro α-glucosidase inhibition. Kinetic studies identified the mode of inhibition, free energy and type of interactions were analyzed through density functional theory and molecular docking. Results & conclusion: Compound 5 was identified as the most potent, noncompetitive and noncytotoxic inhibitor of α-glucosidase enzyme with a half-maximal inhibitory concentration of 24.62 ± 0.94 µM. Computational studies reinforce experimental results, demonstrating significant enzyme interactions via hydrophobic and π-π stacking forces.

Identification of potent compounds against SARs-CoV-2: An in-silico based drug searching against Mpro.

The worldwide pandemic of coronavirus disease 2019 (COVID-19) along with the various newly discovered major SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.1.28, constitute the Variant of Concerns (VOC). It's difficult to keep these variants from spreading over the planet. As a result of these VOCs, the fifth wave has already begun in several countries. The rapid spread of VOCs is posing a serious threat to human civilization. There is currently no specific medicine available for the treatment of COVID-19. Here, we present the findings of methods that used a combination of structure-assisted drug design, virtual screening, and high-throughput screening to swiftly generate lead compounds against Mpro protein of SARs-CoV-2. Therapeutics, in addition to vaccinations, are an essential element of the healthcare response to COVID-19's persistent threat. In the current study, we designed the efficient compounds that may combat all emerging variants of SARs-CoV-2 by targeting the common Mpro protein. The present study was aimed to discover new compounds that may be proposed as new therapeutic agents to treat COVID-19 infection without any adverse effects. For this purpose, a computational-based virtual screening of 352 in-house synthesized compounds library was performed through molecular docking and Molecular Dynamics (MD) simulation approach. As a result, four novel potent compounds were successfully shortlisted by implementing certain pharmacological, physiological, and ADMET criteria i.e., compounds 3, 4, 21, and 22. Furthermore, MD simulations were performed to evaluate the stability and dynamic behavior of these compounds with Mpro complex for about 30 ns. Eventually, compound 22 was found to be highly potent against Mpro protein and was further evaluated by applying 100 ns simulations. Our findings showed that these shortlisted compounds may have potency to treat the COVID-19 infection for which further experimental validation is proposed as part of a follow-up investigation.

Synthesis and Evaluation of Anti-HIV Activity of Mono- and Di-Substituted Phosphonamidate Conjugates of Tenofovir.

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several classes of derivatives were synthesized. The synthesized compounds were characterized by 1H NMR, IR, UV, and mass spectrometry. In addition, several of the synthesized compounds were evaluated as racemic mixtures for anti-HIV activity in vitro in a single round infection assay using TZM-bl cells at 100 ng/mL. TFV (1) was used as a positive control and inhibited HIV infection by 35%. Among all the evaluated compounds, the disubstituted heptanolyl ester alanine phosphonamidate with naphthol oleate (69), pentanolyl ester alanine phosphonamidate with phenol oleate (62), and butanolyl ester alanine phosphonamidate with naphthol oleate (87) ester conjugates of TFV were more potent than parent drug TFV with 79.0%, 76.5%, 71.5% inhibition, respectively, at 100 ng/mL. Furthermore, two fatty acyl amide conjugates of tenofovir alafenamide (TAF) were synthesized and evaluated for comparative studies with TAF and TFV conjugates. Tetradecanoyl TAF conjugate 95 inhibited HIV infection by 99.6% at 100 ng/mL and showed comparable activity to TAF (97-99% inhibition) at 10-100 ng/mL but was more potent than TAF when compared at molar concentration.

Density functional theory calculations of δ(13 C) and δ(1 H) chemical shifts and 3 J(13 COO1 H) coupling constants as structural and analytical tools in hydroperoxides: Prospects and limitations of 1 H13 C heteronuclear multiple bond correlation experiments.

Density functional theory (DFT) calculations of δ(13 C) and δ(1 H) chemical shifts and 3 J(13 COO1 H) coupling constants of three model hydroperoxides of the naturally occurring cis-11-OOH and trans-9-OOH isomers of oleate and 9-cis, 11-trans-16-OOH endo hydroperoxide of methyl linolenate are reported. The computational δ(OOH) for various functionals and basis sets were found to be nearly identical for the cis/trans geometric isomers. The chemical shifts of the methine CHOOH protons and carbons, on the contrary, are highly diagnostic for the identification of cis/trans geometric isomerism. The chemical shifts of the olefinic protons and carbons strongly depend on the orientation of the hydroperoxide unit relative to the double bond and, thus, of importance in conformational analysis. The results are in very good agreement with the available experimental data. For the various diastereomeric pairs of the model endo-hydroperoxide, the strongly deshielded OOH resonances, due to the presence of an intramolecular hydrogen bond between the hydroperoxide proton and an oxygen of the endo-peroxide ring, along with the δ(CHOOH), are highly diagnostic for identification and structure elucidation of complex erythro- and threo- diastereomeric pairs of endo-hydroperoxides; the computational results are in very good agreement with the available experimental data. The 3 J(13 COO1 H) coupling constants were found to be < 2  Hz for the cis-trans geometric models and < 0.5  Hz for the endo-hydroperoxide and, thus, unimportant in stereochemical analysis. Sharp resonances of the hydroperoxide protons, with Δν1/2 < 3 Hz, are required for the successful implementation of the 1 H13 C heteronuclear multiple bond correlation (HMBC) technique.

Identification of quinoline derivatives as growth inhibitors of MDR pathogen Klebsiella pneumoniae.

Aims: This study was aimed to identify compounds with significant inhibitory potential against multidrug-resistant (MDR), multidrug-sensitive and clinical isolates of Klebsiella pneumoniae. Materials & methods: Antibacterial activity of the nitroquinoline derivatives was assessed by micro-plate Alamar Blue assay. Results: Nitroquinoline derivatives 9, 11 and 14 showed inhibitory activity against MDR K. pneumoniae. Docking studies of these compounds with topoisomerase IV of K. pneumonia indicated the interactions of these compounds at the active site residues of enzyme near to cofactor (Mg+2). Furthermore, compound 11 was identified as a reactive oxygen species (ROS) inducer. None of the compounds showed hemolytic effect. Conclusion: This study was designed to identify compounds active against MDR K. pneumoniae which causes infections, such as pneumonia and urinary tract infections.

Microwave assisted Biology-Oriented Drug Synthesis (BIODS) of new N,N'-disubstituted benzylamine analogous of 4-aminoantipyrine against leishmaniasis - In vitro assay and in silico-predicted molecular interactions with key metabolic targets.

Biology-Oriented Drug Synthesis (BIODS) deals with the simple chemical transformations on the commercially available drugs in order to enhance their new and diversified pharmacological profile. It opens new avenues for the rapid development of drug candidates for neglected tropical diseases (NTDs). Leishmaniasis is one of the NTDs which spread by the bite of sandflies (plebotomine). It ranges from cutaneous self-healing leishmaniasis to life threatening visceral leishmaniasis, known as kala-azar. The current treatment options include the use of pentamidine, miltefosine, and amphotericin B drugs. Unfortunately, all currently available drugs are associated with adverse effects, such as severe nephron- and cardiotoxicity, pancreatitis, and hepatotoxicity. This warrants the development of new drugs against leishmaniasis. Moreover, emergence of resistance against the current medications further worsens the conditions. With this objective, new N, N'-disubstituted benzylamine derivatives of ampyrone (4-aminoantipyrine) were synthesized by using ultrasonication, and microwave assistance. All derivatives were found to be new, except 1, 4, and 11. All the compounds were evaluated for their anti-leishmanial activity, and cellular cytotoxicity. Among them, compounds 4, 5, 8, and 9 showed a significant anti-leishmanial activity in vitro, in comparison to standard drug, miltefosine (IC50 = 25.78 ± 0.2 µM). These compounds were also docked against various metabolic enzymes to predict their interactions and mechanism of action, and were found to act via targeting important enzymes of various metabolic pathways.

Synthesis of 1,2,3,triazole modified analogues of hydrochlorothiazide via click chemistry approach and in-vitro α-glucosidase enzyme inhibition studies.

The current study was aimed to discover potent inhibitors of α-glucosidase enzyme. A 25 membered library of new 1,2,3-triazole derivatives of hydrochlorothiazide (1) (HCTZ, a diuretic drug also being used for the treatment of high blood pressure) was synthesized through click chemistry approach. The structures of all derivatives 2-26 were deduced by MS, IR, 1H-NMR, and 13C-NMR spectroscopic techniques. All the compounds were found to be new. Compounds 1-26 were evaluated for α-glucosidase enzyme inhibition activity. Among them, 18 compounds showed potent inhibitory activity against α-glucosidase with IC50 values between 24 and 379 µM. α-Glucosidase inhibitor drug acarbose (IC50 = 875.75 ± 2.08 µM) was used as the standard. Kinetics studies of compounds 6, 9, 11, 12, 15, 20, 23, and 24 revealed that only compound 15 as a mixed-type of inhibitor, while others were non-competitive inhibitors of α-glucosidase enzyme. All the compounds were found to be non-cytotoxic when checked against mouse fibroblast 3T3 cell line.

Synthesis of new Enrofloxacin Derivatives as Potential Antibiofilm Drugs Against Staphylococcus Aureus and Klebsiella Pneumoniae.

BACKGROUND: The antimicrobial resistance due to biofilm formation among bacteria is a significant problem in the healthcare and food industries. OBJECTIVE: The current study describes the synthesis of enrofloxacin derivatives 2-17, and the evaluation of their anti-bacterial and anti-biofilm activities. METHODS: Compounds 2-17 were synthesized through the acylation of enrofloxacin with thionyl chloride, followed by reaction with different aromatic amines. The new analogues identified among the sixteen compounds were 2-7, 11, 14, and 17. RESULTS: Compound 2 appeared to be effective against pathogens S. aureus as well as K. pneumonia, whereas, compound 11 was found active against K. pneumonia only. Compound 2 inhibited >75% biofilm formation of S. aureus at 20 µg/mL and K. pneumonia at 10 µg/mL concentrations. These doses are far below the bactericidal concentration of compound 2, suggesting the anti-virulence mechanism of these compounds. Compound 11 inhibited 60% biofilm formation of K. pneumoniae at 70 µg/mL concentration. Compound 5 inhibited the biofilm of K. pneumoniae at 62 µg/mL concentration but also had bactericidal properties at this concentration. Interestingly, compound 2 eradicated the preformed biofilm of both the pathogens at much lower doses as compared to control drug, gentamycin and substrate, enrofloxacin. Cytotoxicity of compounds 2-17 was checked by a standard method using 3T3 normal cell lines (mouse fibroblast), all compounds were found to be noncytotoxic. CONCLUSION: These compounds can be used alone or with FDA approved drugs to overcome biofilm related K. pneumoniae and S. aureus infections.

Synthesis and Erythroid Induction Activity of New Thiourea Derivatives.

BACKGROUND: The use of medicinal agents to augment the fetal hemoglobin (HbF) accretion is an important approach for the treatment of sickle-cell anemia and ß-thalassemia. HbF inducers have the potential to reduce the clinical symptoms and blood transfusion dependence in the patients of ß- hemoglobinopathies. OBJECTIVE: The current study was aimed to examine the erythroid induction potential of newly synthesized thiourea derivatives. METHODS: Thiourea derivatives 1-27 were synthesized by using environmentally friendly methods. Compounds 3, 10 and 22 were found to be new. The structures of synthesized derivatives were deduced by using various spectroscopic techniques. These derivatives were then evaluated for their erythroid induction using the human erythroleukemic K562 cell line, as a model. The benzidine-H2O2 assay was used to evaluate erythroid induction, while HbF expression was studied through immunocytochemistry using the Anti-HbF antibody. Cytotoxicity of compounds 1-27 was also evaluated on mouse fibroblast 3T3 cell line and cancer Hela cell line using MTT assay. RESULT: All the compounds (1-27) have not been reported for their erythroid induction activity previously. Compounds 1, 2, and 3 were found to be the potent erythroid inducing agents with % induction of 45± 6.9, 44± 5.9, and 41± 6.1, at 1.56, 0.78, and 0.78 µM concentrations, respectively, as compared to untreated control (12 ± 1 % induction). Furthermore, compound 1, 2, and 3 significantly induced fetal hemoglobin the expression up to 4.2-fold, 4.06-fold, and 3.52-fold, respectively, as compared to untreated control. Moreover, the compounds 1-4, 6-9, 11, 12, 15, 17, 19, 22, 23, and 25 were found to be non-cytotoxic against the 3T3 cell line. CONCLUSION: This study signifies that the compounds reported here may serve as the starting point for the designing and development of new fetal hemoglobin inducers for the treatment of ß- hemoglobinopathies.

Synthesis, crystal structure and Hirshfeld Surface analysis of benzamide derivatives of thiourea as potent inhibitors of α-glucosidase in-vitro.

Benzamide based structural analogues 1-15 were synthesized, and evaluated for α-glucosidase inhibition activity in vitro for the first time. Compounds 1-9 were found to be known, while compounds 10-15 were found to be new. However, to the best of our knowledge we are reporting α-glucosidase inhibitory activity of these bezamide derivatives of thiourea for the first time. Compounds 1, 3, 6-8, 10-14 were found to be potent inhibitors of α-glucosidase within IC50 range of 20.44-333.41 µM, in comparison to the standard inhibitor, acarbose (IC50 = 875.75 ± 2.08 µM). Mode of the enzyme inhibition was determined on the basis of kinetic studies which demonstrated that compounds 8, and 10 were non-competitive and competitive inhibitors of α-glucosidase enzyme, respectively. These compounds were also evaluated for their DPPH radical scavenging activity, and cytotoxicity against 3T3 mouse fibroblast cell lines. All synthesized compounds showed a significant to moderate DPPH radical scavenging activity and appeared to be non-cytotoxic except compound 9 which showed cytotoxicity against 3T3 normal mouse fibroblast cell lines. A single crystal X-ray and Hirshfeld Surface analysis of a representative compound is also presented.

NMR and Computational Studies as Analytical and High-Resolution Structural Tool for Complex Hydroperoxides and Diastereomeric Endo-Hydroperoxides of Fatty Acids in Solution-Exemplified by Methyl Linolenate.

A combination of selective 1D Total Correlation Spectroscopy (TOCSY) and 1H-13C Heteronuclear Multiple Bond Correlation (HMBC) NMR techniques has been employed for the identification of methyl linolenate primary oxidation products without the need for laborious isolation of the individual compounds. Complex hydroperoxides and diastereomeric endo-hydroperoxides were identified and quantified. Strongly deshielded C-O-O-H 1H-NMR resonances of diastereomeric endo-hydroperoxides in the region of 8.8 to 9.6 ppm were shown to be due to intramolecular hydrogen bonding interactions of the hydroperoxide proton with an oxygen atom of the five-member endo-peroxide ring. These strongly deshielded resonances were utilized as a new method to derive, for the first time, three-dimensional structures with an assignment of pairs of diastereomers in solution with the combined use of 1H-NMR chemical shifts, Density Functional Theory (DFT), and Our N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) calculations.

Tyramine Derivatives as Potent Therapeutics for Type 2 Diabetes: Synthesis and In Vitro Inhibition of α-Glucosidase Enzyme.

BACKGROUND: Tyramine derivatives 3-16 were prepared and tested first time for their α- glucosidase (Sources: Saccharomyces cerevisiae) inhibitory activity by using an in vitro mechanismbased biochemical assay. All the compounds were found to be new, except compounds 3, 10-12 and 16. OBJECTIVE: In continuation of our research to synthesize and identify potent inhibitors of α-glucosidase enzyme, we intended to synthesize new inhibitors of α-glucosidase enzyme with enhanced efficacy in order to provide the basis for the better treatment of the type-II diabetic. METHODS: Tyramine (1) was allowed to react with a variety of aryl chlorides (2) to yield the corresponding amides. Synthesized compounds were then purified through normal phase column chromatography. Compounds 3-16 were then assessed for their α-glucosidase inhibitory activity in an in vitro biochemical assay. The cytotoxicity of compounds 3-16 was determined by using 3T3 mouse fibroblast cell lines. RESULTS: Compounds 3-5, 8, 13, and 15-16 were found to be more active (IC50 = 103.1±0.46, 37.3±4.51, 56.7±4.2, 23.9±2.31, 43.6±2.88, 55.8±1.73, and 38.2±0.86 µM, respectively) than the acarbose, the standard inhibitor of α-glucosidase enzyme, (IC50= 840.0±1.73 µM). To determine the dissociation constants and mode of inhibition, the kinetic studies were also performed for compounds 4 and 8 (the most potent inhibitors). It was observed that compounds 4 and 8 possess noncompetitive properties as the inhibitors of α-glucosidase. All the compounds were found to be noncytotoxic, except 5 and 12 (IC50= 14.7± 0.24 and 6.6± 0.38 µM, respectively). CONCLUSION: The current study gives the facile synthesis and identification of potent inhibitors of α- glucosidase. The new inhibitors reported here may be investigated further for the designing and development of novel anti-diabetic agents.

Chemical constituents from Parrotia persica- Structural derivatization and their potential prolyl endopeptidase inhibition activity.

The current study was aimed to evaluate the prolyl endopeptidase (PEP) inhibitory activity of glutinol (1), azadiradione (2), quercetin 3-O-ß-d-glactopyranoside (3), catechin (4), quercetin (5), naringenin (6) isolated from Parrotia persica C. A. Mey. Naringenin (6) was further derivatized into 7-O-propargylnaringenin (7), 4',6',4″-O-propargylchalcone (8), and 4',4″-O-propargylchalcone (9). All compounds 1-9 were evaluated for their PEP inhibition activity. PEP is associated with several diseases, including dementia, and Alzheimer's disease (AD). Azadiradione (2) was less active with IC50 = 356.80 ± 2.9 µM, whereas quercetin (5) showed a potent activity with IC50 = 37.12 ± 2.2 µM, as compared to IC50 = 125.00 ± 1.5 µM of standard drug bacitracin. Naringenin (6) was found to be inactive, whereas its new analogues 7-9 were identified as potent inhibitors of PEP with IC50 = 35.20, 41.20, and 29.60 µM, respectively. Kinetic studies of active compounds indicated their modes of inhibition. Compounds 7-9 were found to be mixed-type inhibitors, while compound 5 was found to be non-competitive inhibitor.

Crystal structure and Hirshfeld surface analysis of N-(2-chloro-phenyl-carbamo-thio-yl)-4-fluoro-benzamide and N-(4-bromo-phenyl-carbamo-thio-yl)-4-fluoro-benzamide.

The title compounds, C14H10ClFN2OS (1) and C14H10BrFN2OS (2), were synthesized by two-step reactions. The dihedral angles between the aromatic rings are 31.99 (3) and 9.17 (5)° for 1 and 2, respectively. Compound 1 features an intra-molecular bifurcated N-H⋯(O,Cl) link due to the presence of the ortho-Cl atom on the benzene ring, whereas 2 features an intra-molecular N-H⋯O hydrogen bond. In the crystal of 1, inversion dimers linked by pairs of N-H⋯S hydrogen bonds generate R 2 2(8) loops. The extended structure of 2 features the same motif but an additional weak C-H⋯S inter-action links the inversion dimers into [100] double columns. Hirshfeld surface analyses indicate that the most important contributors towards the crystal packing are H⋯H (26.6%), S⋯H/H.·S (13.8%) and Cl⋯H/H⋯Cl (9.5%) contacts for 1 and H⋯H (19.7%), C⋯H/H⋯C (14.8%) and Br⋯H/H⋯Br (12.4%) contacts for 2.