Synthesis and biological screening of new thiazolo[4,5-d]pyrimidine and dithiazolo[3,2-a:5′,4′-e]pyrimidinone derivatives as antimicrobial,antiquorum-sensing and antitumor agents

New thiazolopyrimidine and dithiazolopyrimidinone derivatives 2–11 were synthesized and estimated for antimicrobial activity against S. aureus, B. cereus, E. coli, C. albicans, A. fumigatus and A. terreus. The attained results proved that 4, 8a and 11g have significant effectiveness against S. aureus and B. cereus. On the other hand, 7, 10b, 10c and 11h exhibited prominent activity against B. cereus, whereas 8a, 10b and 11g were proved to be active against E. coli. From another point of view, 4 and 8a exhibited promising efficacy against A. fumigatus and A. terreus; moreover, 8a showed outstanding efficacy against C. albicans. Quorum-sensing inhibitory activity of the new compounds was esteemed against C. violaceum, where 7, 8a, 9b, 10a-c, 11d and 11g have acceptable efficacy. In vitro antitumor efficacy of the same compounds against HepG2, HCT-116 and MCF-7 cancer cell lines was also tested. Compounds 4 and 11h showed enhanced effectiveness against the three cell lines, whereas 10b displayed eminent activity against HCT-116 and MCF-7 cells. Moreover, 11a was found to have outstanding activity against MCF-7 cells, while 11i showed promising efficacy against HepG2 cells. The in vitro active antitumor compounds were evaluated for in vivo antitumor effectiveness against EAC in mice, as well as in vitro cytotoxicity against WI38 and WISH normal cells. Results manifested that 4 has the strongest in vivo activity, and that all investigated analogs are less cytotoxic than 5-FU against both normal cell lines. DNA-binding affinity of the active compounds was examined, where 4, 8a, 10c, 11d and 11g,h displayed strong affinity. In silico studies proved that majority of the analyzed compounds are in conformity with the optimum needs for good oral absorption.     

The novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of N-aryl urea: synthesis, anti-inflammatory, antibacterial and antifungal activity evaluation

A series of novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of biological interest were prepared by sequential Bigineli’s reaction, reduction followed by reaction of resulting amines with different arylisocynates. All the synthesized (1-23) compounds were screened against the pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological activity evaluation study reveled that among all the compounds screened, compounds 12 and 17 found to have promising anti-inflammatory activity (68-62% TNF-α and 92-86% IL-6 inhibitory activity at 10 μM). Interestingly compounds 3, 4, 5, 6, 15, 22 and 23 revealed promising antimicrobial activity at MIC of 10-30 μg/mL against selected pathogenic bacteria and fungi.     

Synthesis and biological evaluation of a new series of N-acyldiamines as potential antibacterial and antifungal agents

In continuation of our efforts to find new antimicrobial compounds, series of fatty N-acyldiamines were prepared from fatty methyl esters and 1,2-ethylenediamine, 1,3-propanediamine or 1,4-butanediamine. The synthesized compounds were screened for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and for their antifungal activity against four species of Candida (C. albicans, C. tropicalis, C. glabrata and C. parapsilosis). Compounds 5a (N-(2-aminoethyl)dodecanamide), 5b (N-(2-aminoethyl)tetracanamide) and 6d (N-(3-aminopropyl)oleamide) were the most active against Gram-positive bacteria, with MIC values ranging from 1 to 16 μg/mL and were evaluated for their activity against 21 clinical isolates of methicillin-resistant S. aureus. All the compounds exhibited good to moderate antifungal activity. Compared to chloramphenicol, compound 6b displayed a similar activity (MIC₅₀ = 16 μg/mL). A positive correlation could be established between lipophilicity and biological activity.     

Synthesis and antimicrobial activities of halogenated bis(hydroxyphenyl)methanes

A series of halophenols was prepared by the reaction of bis(hydroxyphenyl)methanes with effective halogenating agents such as bromine and sulfuryl chloride. One of these compounds, a biologically active halophenol—2,2′,3,3′-tetrabromo-4,4′,5,5′-tetrahydroxydiphenylmethane (1)—frequently isolated from red algae, was synthesized for the first time. Other halophenols included several novel compounds, together with known derivatives that were synthesized from the phenolic intermediates, bis(3,4-dihydroxyphenyl)methane (5) and bis(2-hydroxyphenyl)methane (14). All of the synthesized compounds were tested for antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. The preliminary structure–activity relationship was investigated in order to determine the essential structural requirements for their antimicrobial activity. Of all these halophenols, 2,2′,3,3′,6-pentabromo-4,4′,5,5′-tetrahydroxydiphenylmethane (8) was found to be the most active against Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, and Trichophyton mentagrophytes while 3,3′,5,5′-tetrachloro-2,2′-dihydroxydiphenylmethane (18) exerted a powerful antibacterial effect against Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Proteus vulgaris, and Salmonella typhimurium.     

Synthesis,characterization, in vitro cytotoxicity and antimicrobial investigation and evaluation of physicochemical properties of novel 4-(2-methylacetamide)benzenesulfonamide derivatives

In this study, several sulfonamide derivatives, 4-(2-methylacetylamino)benzenesulfonamides were synthesized. Chemical structures of the derivatives were characterized by ¹H NMR, ¹³C NMR, LC–MS–MS, UV–Vis, FTIR, photoluminescence and elemental analysis. Sulfanilamide was reacted with 2-bromopropionyl bromide, in the presence of pyridine, to form bromo-substituted sulfonamide key intermediates, which were subsequently treated with secondary amines to obtain novel sulfonamide derivatives. All the synthesized compounds were evaluated for in vitro antimicrobial activities and cytotoxicity. Increases in ring size, and rings bearing a nitrogen heteroatom led to improvements in antimicrobial activities. As the presence of CA IX and CA XII enzymes have been implicated in some cancerous tumors, the studies presented herein focuses on targeting these enzymes. It was found that the synthesized derivatives had in vitro anti-cancer properties, where compounds (3–6) were found to be active against all cancerous cells, and no cytotoxic effects on normal cells were observed.     

Synthesis,antimicrobial, antioxidant,cytotoxic, antiurease and molecular docking studies of N-(3-trifluoromethyl)benzoyl-N′-aryl thiourea derivatives

An irrefutable advancement has been noted for the infectious diseases caused due to ureolytic bacteria through the development of various drugs. Keeping in mind the extremely valuable synthetic utility and medicinal significance of thiourea derivatives, synthesis of new 3-trifluoromethyl benzoic acid thiourea derivatives (3a–j) were carried out. The biological potential of all compounds in terms of antimicrobial, antioxidant, cytotoxic and antiurease activities were studied. The compounds 3a, 3c and 3i with dichloro and methoxy groups substitution on the aryl group showed significant activity against all strain of bacteria while moderate to no activity was observed in remaining compounds. Whereas the antifungal evaluation showed that all compounds were active againts C. Albican and no activity was observed against C. Prapsilosis. The cytotoxic findings revealed the non-toxic nature of these compounds as IC₅₀ values of majority of the compounds are above 100 μm except for compounds 3f and 3g. In addition, these compounds exhibited better antioxidant potential as 100 μm concentration inhibited >50% reactive oxygen species (ROS) production except compounds 3e, 3f and 3j. The compound 3a proved to be the most potent urease inhibitor showing the highest enzyme % inhibition (93.1%) with IC₅₀ value of 8.17 ± 0.24 µM and found more active as compare to standard followed by compound 3e (92.6%), 3h (91.6%), 3d (90.8%), 3b (90.6%) and 3f (90.0%) with their respective IC₅₀ values. All the synthesized compounds were docked into the binding cavity of Urease (PDB ID: 4ubp). The most active compound 3a was also ranked as top on the docking score as it was found to show valuable interactions with the target protein along with good docking scores. Hence our results revealed that the synthesized compounds have potential to be used as potent urease inhibitors after further detailed mechanistic studies.     

Synthesis and biological evaluation of isoxazolyl-sulfonamides: A non-cytotoxic scaffold active against Trypanosoma cruzi, Leishmania amazonensis and Herpes Simplex Virus

In this study we report the synthesis, characterization, biological evaluation, and druglikeness assessment of a series of 20 novel isoxazolyl-sulfonamides, obtained by a four-step synthetic route. The compounds had their activity against Trypanosoma cruzi, Leishmania amazonensis, Herpes Simplex Virus type 1 and cytotoxicity evaluated in phenotypic assays. All compounds have drug-like properties, showed low cytotoxicity and were promising regarding all other biological activities reported herein, especially the inhibitory activity against T. cruzi. The compounds 8 and 16 showed significant potency and selectivity against T. cruzi (GI₅₀?=?14.3?µM, SI?>?34.8 and GI₅₀?=?11.6?µM, SI?=?29.1, respectively). These values, close to the values of the reference drug benznidazole (GI₅₀?=?10.2?µM), suggest that compounds 8 and 16 represent promising candidates for further pre-clinical development targeting Chagas disease.     

One pot three components microwave assisted and conventional synthesis of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one as antimicrobial agents

A one-pot, three-component, microwave assisted and conventional synthesis of new 3-(4-chloro-2-hydroxyphenyl)-2-(substituted) thiazolidin-4-one (4a–n) was carried out by using N,N-dimethylformamide as a solvent with high product yield. Among these synthesized compounds (4f, 4g, 4l and 4m) were found to be a broad spectrum molecule active against all bacterial and fungus strains tested, except fungus Aspergillus niger. Amongst the compounds (4g, 4l and 4m) were found to be more potent than respective standard drugs used in the experiment against Candida albicans, Staphylococcus aureus and Aspergillus flavus, respectively. All synthesized compounds were also tested for their cytotoxic activity against HeLa and MCF-7 cell lines by the sulforhodamine B (SRB) assay. This study shows that all compounds were non-cytotoxic in nature, and confirmed their antimicrobial specificity apart from any general cytotoxicity.     

Hydroxyl alkyl ammonium ionic liquid assisted green and one-pot regioselective access to functionalized pyrazolodihydropyridine core and their pharmacological evaluation

Herein our team explored a promising synthetic trail to Functionalized pyrazolodihydropyridine core using hydroxyl alkyl ammonium ionic liquid via one-pot fusion of 3-methyl-1-phenyl-1H-pyrazole-5-amine, different heterocyclic aldehydes and 1, 3-Cyclic diones. The aimed compounds were obtained by Domino-Knoevenagel condensation and Michael addition followed by cyclization. The reaction transformation involves the formation of two CC and one CN bond formation. The perspective of the present work is selectively approached to Functionalized pyrazolodihydropyridine core excluding other potential parallel reactions under environmentally benign reaction condition. The present protocol show features such as the low E-factor, ambiphilic behavior of ionic liquid during reaction transformation, scale-up to a multigram scale, reusability of the ionic liquid, mild reaction condition, and produce water as a byproduct. All newly derived compounds were evaluated for their in vitro biological activities. In preliminary biological studies compound, 4c showed better potency than the standard drug ampicillin against Gram-negative bacteria (E. coli); the compound 4i exhibited outstanding activity against S. aeruginosa which is far better than ampicillin, chloramphenicol, and ciprofloxacin. The compound 4m was found more potent against C. albicans, than that of griseofulvin and show equipotency to nystatin whereas, in preliminary antitubercular screening, compound 4o was exhibited more potency than rifampicin. Noteworthy compounds 4f and 4i were found most active in antiproliferative screening.     

Stereoselective synthesis of enantiopure N-substituted pyrrolidin-2,5-dione derivatives by 1,3-dipolar cycloaddition and assessment of their in vitro antioxidant and antibacterial activities

1,3-Dipolar cycloaddition between a chiral nitrone and N-substituted maleimides afforded unprecedented enantiopure spiro-fused heterocycles in good yields with a high enantio- and diastereoselectivity. The reaction was taking place on the less hindered face of the nitrone. The obtaining heterocycles were screened for their in vitro antioxidant properties and the results revealed that the potent antioxidant activity was generally recorded to compounds (3g) and (3e). The in vitro antibacterial activities of these two compounds were also investigated and the results demonstrated the strongest potential of compound (3g) against all the tested bacteria. Molecular properties were analyzed and showed good oral drug candidate like properties and that could be exploited as a potential antioxidant and antimicrobial agent. Finally, the preliminary results obtained from this investigation attempted to clarify if the structurally different side chains of active compounds interfere with their biological properties.     

Synthesis and SAR study of novel anticancer and antimicrobial naphthoquinone amide derivatives

A series of novel naphthoquinone amide derivatives of the bioactive quinones, plumbagin, juglone, menadione and lawsone, with various amino acids were synthesized. The compounds were characterized by ¹H NMR, ¹³C NMR, Mass, IR and elemental analysis. All the compounds were evaluated for their anticancer activity against HeLa and SAS cancer cell lines and 3D-QSAR indicated the presence of electron donating group near sulphur enhanced the activity against HeLa cells. Among the derivatives synthesized, compounds 11f, 10a, 10b and 10g were the most active with IC₅₀ values of 16, 12, 14 and 24.5 μM, respectively. The analogues were also screened for antimicrobial activity against two human bacterial pathogens, the Gram-positive Methicillin resistant Staphylococcus aureus (MRSA) and the Gram-negative Pseudomonas aeruginosa and a human yeast pathogen, Fluconazole resistant Candida albicans (FRCA). Among the synthesized compounds, 8g, 10g and 11g exhibited maximum antibacterial activity towards MRSA and antifungal activity against FRCA in well diffusion method.     

Efficient synthesis and antimicrobial activity of some novel S-β-d-glucosides of 5-aryl-1,2,4-triazole-3-thiones derivatives

A series of 3-S-β-d-glucosides-4-arylideneamino-5-aryl-1,2,4-triazoles were rationally designed and synthesized according to the principle of superposition of bioactive substructures by the combination of 1,2,4-triazole, Schiff base and glucosides. The structures of the target compounds have been characterized by ¹H NMR, ¹³C NMR, IR, MS and HRMS. All the newly synthesized compounds have been evaluated for their antimicrobial activities in vitro against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8099) as well as Monilia albican (ATCC 10231). The bioactive assay showed that most of the tested compounds displayed variable inhibitory effects on the growth of the Gram-positive bacterial strain (Staphylococcus aureus), Gram-negative bacterial strains (Escherichia coli) and fungal strains (Monilia albican). All the target compounds exhibited better antifungal activity than antibacterial activity. Especially, compounds 6b, 6c, 6f, 6j, 6k and 6l showed excellent activity against fungus Monilia albican with MIC values of 16 μg/mL.     

Azole antimicrobial pharmacophore-based tetrazoles: Synthesis and biological evaluation as potential antimicrobial and anticonvulsant agents

The azole pharmacophore is still considered a viable lead structure for the synthesis of more efficacious and broad spectrum antimicrobial agents. Potential antibacterial and antifungal activities are encountered with some tetrazoles. Therefore, this study presents the synthesis and antimicrobial evaluation of a new series of substituted tetrazoles that are structurally related to the famous antimicrobial azole pharmacophore. A detailed discussion of the structural elucidation of some of the newly synthesized compounds is also described. Antimicrobial evaluation revealed that twenty compounds were able to display variable growth inhibitory effects on the tested Gram positive and Gram negative bacteria with special efficacy against the Gram positive strains. Meanwhile, six compounds exhibited moderate antifungal activity against Candida albicans and Aspergillus fumigatus. Structurally, the antibacterial activity was encountered with tetrazoles containing a phenyl substituent, while the obtained antifungal activity was confined to the benzyl variants. Compounds 16, 18, 24 and 27 were proved to be the most active antibacterial members within this study with a considerable broad spectrum against all the Gram positive and negative strains tested. A distinctive anti-Gram positive activity was displayed by compound 18 against Staphylococcus aureus that was equipotent to ampicillin (MIC 6.25 μg/mL).On the other hand, twelve compounds were selected to be screened for their preliminary anticonvulsant activity against subcutaneous metrazole (ScMet) and maximal electroshock (MES) induced seizures in mice. The results revealed that five compounds namely; 3, 5, 13, 21, and 24 were able to display noticeable anticonvulsant activity in both tests at 100 mg/kg dose level. Compounds 5 and 21 were proved to be the most active anticonvulsant members in this study with special high activity in the ScMet assay (% protection: 100% and 80%, respectively).     

Design,synthesis and molecular modeling studies on novel moxifloxacin derivatives as potential antibacterial and antituberculosis agents

Twenty-one novel alkyl/acyl/sulfonyl substituted fluoroquinolone derivatives were designed, synthesized and evaluated for their anti-tuberculosis and antibacterial activity. The targeted compounds were synthesized by the introduction of alkyl, acyl or sulfonyl moieties to the basic secondary amine moiety of moxifloxacin. Structures of the compounds were enlightened by FT-IR, ¹H NMR, ¹³C NMR and HRMS data besides elemental analysis. Compounds were initially tested in vitro for their anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv using microplate alamar blue assay. Minimal inhibitory concentration (MIC) values of all compounds were found between > 25.00–0.39 µg/mL while compounds 1, 2 and 13 revealed an outstanding activity against M. tuberculosis H37Rv with MIC values of 0.39 µg/mL. Activities of compounds 1–21 against to a number of Gram-positive and Gram-negative bacteria and fast growing mycobacterium strain were also investigated by agar well diffusion and microdilution methods. According to antimicrobial activity results, compound 13 was found the most potent derivative with a IC₅₀ value of <1.23 μg/mL against Staphylococcus aureus and clinical strain of methicillin-resistant clinical strain of S. aureus.     

New amide linked dimeric 1,2,3-triazoles bearing aryloxy scaffolds as a potent antiproliferative agents and EGFR tyrosine kinase phosphorylation inhibitors

A search for potent antiproliferative agents has prompted to design and synthesize aryloxy bridged and amide linked dimeric 1,2,3-triazoles (7a–j) by using 1,3-dipolar cycloaddition reaction between 2-azido-N-phenylacetamides (4a–e) and bis(prop-2-yn-1-yloxy)benzenes (6a–b) via copper (I)-catalyzed click chemistry approach with good to excellent yields. All the newly synthesized compounds have been screened for their in vitro antiproliferative activities against two human cancer cell lines. The compounds 7d, 7e, 7h, 7i and 7j have revealed promising antiproliferative activity against human breast cancer cell line (MCF-7), whereas, the compounds 7a, 7b, 7c, 7i and 7j were observed as potent antiproliferative agents against human lung cancer cell line (A-549). The active compounds against MCF-7 have been also analysed for their mechanism of action by the enzymatic study, which shows that the compounds 7d, 7h and 7j were acts as active EGFR tyrosine kinase phosphorylation inhibitors. In support to this biological study, the molecular docking as well as in silico ADME properties of all the newly synthesized hybrids were predicted.     

Synthesis and biological evaluation of tetrazole derivatives as TNF-α, IL-6 and COX-2 inhibitors with antimicrobial activity: Computational analysis,molecular modeling study and region-specific cyclization using 2D NMR tools

A group of tetrazole bearing compounds were synthesized and evaluated for their in vitro cyclooxygenase (COX) isozymes (COX-1/COX-2) inhibitory activity, in vitro anti-inflammatory activity through measuring levels of expression of IL-6 and TNF-α and antimicrobial activity. Cyclization of pyridine derivative 5b was confirmed using 2D NMR such as NOESY and HMBC experiments. Within the synthesized compounds, compound 7c was identified as effective and selective COX-2 inhibitors (COX-2 IC₅₀ = 0.23 uM; COX-2 selectivity index = 16.91). Moreover 7c was the most effective derivative on TNF-α (37.6 pg/ml). While, the most active compound on IL-6 was isoxazole derivative 6 (42.8 pg/ml). Dual inhibitory activity on both IL-6 and TNF-α was exhibited by compounds 2 and 3 (IL-6 = 47.5 and 82.7 pg/ml, respectively) and (TNF-α = 31.7 and 33.8 pg/ml, sequentially).Additionally, compound 7a, showed broad spectrum antimicrobial activity against Gram positive cocci, Gram positive rods and yeast fungus (inhibition zone = 20 and 19 mm). None of the test compounds exhibited activity against Gram negative rods. Compounds 3 and 7c exhibited good antifungal activity at MIC equal to 64.5 µg/ml. While compound 6 showed antibacterial activities against Micrococcus lysodicticus and Bacillus subtilis at MIC = 32.25 and 64.5 µg/ml, respectively.Computational analysis was used to predict molecular properties and bioactivity of the target compounds. To confirm the mode of action of the synthesized compounds as anti-inflammatory agents, molecular docking was done. Appreciable binding interactions were observed for compound 7c containing COX-2 pharmacophore (SO₂NH₂), with binding energy −10.6652 Kcal/mol, forming two hydrogen bonding interactions with His90 and Tyr355 amino acids. It was fully fitted within COX-2 active site having the highest COX-2 selectivity index between all the test compounds (S.I. = 16.91).     

Ultrasonication-ionic liquid synergy for the synthesis of new potent anti-tuberculosis 1,2,4-triazol-1-yl-pyrazole based spirooxindolopyrrolizidines

The aim of the study is to design and synthesis of a new series of potent anti-TB 1,2,4-triazol-1-yl-pyrazole based spirooxindolopyrrolizidines with their safety profile. A synergetic effect of ultrasonication and ionic liquid was shown successfully as a green methodology for the synthesis of title compounds 6a–t. These derivatives were obtained in shorter reaction time with good yields and well characterized by various spectroscopic methods, single-crystal X-ray diffraction (6f). The in vitro anti-tuberculosis activity for newly-synthesized derivatives has been screened against Mycobacterium tuberculosis. Among all, six compounds 6e, 6k, 6l, 6n, 6q and 6r exhibited equal potent activity compared to standard drug ethambutol (MIC: 1.56 µg/mL) and another compound 6h exhibited outstanding activity (MIC: 0.78 µg/mL) than the standard drug ethambutol. Cytotoxic nature of the anti-TB active compounds was evaluated against RAW 264.7 cells. The 6h, 6e, 6k, 6l, 6n, 6q and 6r exhibited lower toxicity which could be promising hits for anti-tuberculosis.     

Amino acids conjugated quinazolinone-Schiff’s bases as potential antimicrobial agents: Synthesis,SAR and molecular docking studies

A series of amino acids conjugated quinazolinone-Schiff’s bases were synthesized and characterized by analytical and spectroscopic methods. All the synthesized analogues (8–43) and the intermediates (1–7) were screened for their in vitro antibacterial and antifungal activities. In antimicrobial activity, compounds 12–16, 21–25, 30–34 and 39–43 showed excellent antibacterial activity which is better than the antibacterial standard Streptomycin. Compounds 15, 23–25, 30–34, 36 and 38–43 showed excellent antifungal activities which is more active than the reference antifungal drug Bavistin. Further, to understand the correlation of biological activity with that of drug-receptor interaction, molecular docking was performed on active site ofglucosamine-6-Phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) which showed good binding profile. Molecular docking studies and Preliminary structure-activity (SAR) relationship revealed that the tryptophan and phenylalanine conjugated quinazolinones with electron donating groups (OH and OCH₃) were found to be excellent antimicrobial activities which is better than the glycine and alanine conjugated derivatives. This may be explained by the contribution of aromaticity and hydrophobicity of amino acids. Among the series, compounds 41 and 43 showed the highest docking scores for antimicrobial activity. The conjugation plays a major role in improving the biological activities of those compounds.     

A new δ-tocotrienolic acid derivative and other constituents from the cones of Cedrus atlantica and their in vitro antimicrobial activity

The phytochemical and antimicrobial properties of the cones of Cedrus atlantica (Endl) Manetti ex Carrière were investigated. Two new compounds (1,2) and nineteen known compounds (3–21) were isolated. Their structures were established by mass spectrometry (HRESIMS), 1D, 2D NMR and by comparison with literature data. Antimicrobial activity of hydromethanolic extract against a panel of 22 bacteria and yeasts showed an interesting antimicrobial activity. All compound purified from this extract were tested against S. aureus by bioautography. MIC values of the most active compounds were determined using a serial dilution technique. The results showed strong antibacterial activity of the abietane diterpenes 10, 11, 14, 15, 16 and 17. Dehydroabietic acid (17) was the most potent against Enterococcus faecalis (MIC = 15.1 = μg/mL), a multi-resistant commensal bacterium which can cause the fatal infections in humans.     

5-Adamantan thiadiazole-based thiazolidinones as antimicrobial agents. Design,synthesis, molecular docking and evaluation

In continuation of our efforts to develop new compounds with antimicrobial properties we describe design, synthesis, molecular docking study and evaluation of antimicrobial activity of seventeen novel 2-{[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-imino}-5-arylidene-1,3-thiazolidin-4-ones. All compounds showed antibacterial activity against eight Gram positive and Gram negative bacterial species. Twelve out of seventeen compounds were more potent than streptomycin and all compounds exhibited higher potency than ampicillin. Compounds were also tested against three resistant bacterial strains: MRSA, P. aeruginosa and E. coli. The best antibacterial potential against ATCC and resistant strains was observed for compound 8 (2-{[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-imino}-5-(4-nitrobenzylidene)-1,3thiazolidin-4-one). The most sensitive bacterium appeared to be S. typhimirium, followed by B. cereus while L. monocitogenes and M. flavus were the most resistant. Compounds were also tested for their antifungal activity against eight fungal species. All compounds exhibited antifungal activity better than the reference drugs bifonazole and ketokonazole (3-115 times). It was found that compound 8 appeared again to be the most potent. Molecular docking studies on E. coli MurB, MurA as well as C. albicans CYP 51 and dihydrofolate reductase were used for the prediction of mechanism of antibacterial and antifungal activities confirming the experimental results.