Search

A series of 1,3-diphenylpyrazole-chromenoquinolin-6-one compounds were designed and synthesized by using a greener and recyclable heterogeneous Amberlite IR-120H resin as a catalyst, in the presence of ethanol reflux conditions. Interestingly, the catalyst can be recovered after completion of the reaction and can be reused without loss of catalytic property. Therefore, this method provides a green and environmentally benign much improved protocol for the synthesis of 1,3-diphenylpyrazolechromenoquinolin-6-one compounds. The synthesized library of thirty compounds were tested against their cytotoxicity; moreover, the compounds 5s and 5t exhibited potential cytotoxic activity with IC50 values of 1.22 and 1.64 µM, respectively, on MCF-7 cancer cells. The biophysical studies such as UV-visible, fluorescence and circular dichroism studies indicate that these compounds possess good DNA intercalation ability. In addition, these compounds efficiently inhibit topoisomerase I activity. Molecular docking and viscosity studies support that these compounds exhibited intercalative mode of binding with DNA.

Herein, we have designed and synthesized new imidazo[2,1-b]thiazole-based aryl hydrazones (9a-w) and evaluated their anti-proliferative potential against a panel of human cancer cell lines. Among the synthesized compounds, 9i and 9m elicited promising cytotoxicity against the breast cancer cell line MDA-MB-231 with IC50 values of 1.65 and 1.12 μM, respectively. Cell cycle analysis revealed that 9i and 9m significantly arrest MDA-MB-231 cells in the G0/G1 phase. In addition, detailed biological studies such as annexin V-FITC/propidium iodide, DCFH-DA, JC-1 and DAPI staining assays revealed that 9i and 9m triggered apoptosis in MDA-MB-213 cells. Overall, the current work demonstrated the cytotoxicity and apoptosis-inducing potential of 9i and 9m in breast cancer cells and suggested that they could be explored as promising antiproliferative leads in the future.

Indenopyrazole is emerging as one of the most promising and privileged scaffold in medicinal chemistry. This scaffold have been investigated for the development of novel derivatives and hybrids with other moieties and substituents exhibiting a wide range of medicinal properties like antimycobacterial, antipsychotic, antihypertensive, cannabinoid receptor affinity, anti-tumor, antimicrobial, etc. Furthermore, indenopyrazoles function as inhibitors in various mechanistic pathways which has been well established based on its anticancer potential. This review illustrates various synthetic strategies adopted and reveals the extensive significant biological properties of indenopyrazoles. Furthermore, ample scope is available for this scaffold which needs to be explored by medicinal chemists for the development of new potential drug candidates.

Two series of N-2-benzothiazolyl-4-(arylsulfonyl)-1-piperazineacetamides/propanamides were synthesized from substituted 2-aminobenzothiazoles and were assayed for their in vitro antimicrobial activities against a panel of different pathogenic bacterial strains such as Micrococcus luteus, S. aureus, S. aureus MLS-16, B. subtilis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella planticola and Candida albicans. Among the synthesized compounds 5e,f,g and 6g,h,i showed promising antifungal activity against C. albicans as compared to the reference drug, miconazole. Further, compounds 6g,h,i showed broad spectrum antibacterial activity against all the tested bacterial strains, while the compounds 6a-f,j-m showed significant antibacterial activity against all the tested bacterial strains as compared to the reference drug, ciprofloxacin. In addition, the target compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity, and, among the tested, compounds 5j,k,l and 6i showed promising AChE inhibitory activity.

Recent attention on marine microbes has gained a renewed interest on natural product-based drug discovery with functional potential. Nevertheless, marine yeasts were less explored from a bioindustrial and biomedical perspective, especially on biosurfactants regardless no novel structures were identified till date. Considering these facts, this study screened biosurfactants from marine yeasts having broad spectrum industrial significance with the basic tensioactive properties, emulsification and non-hemolytic activities. Among the 136 strains isolated from three different stations of Tamil Nadu, India, Cyberlindnera saturnus SBPN-27 exhibited promising features. The biosurfactant from this marine yeast was purified and structurally characterized as Gal-Gal-Gal-Heptadecanoic acid (named as Cybersan) based on different spectral analysis. Further, Cybersan revealed surface tension of 28 mN m−1 at critical micelle concentration of 30 mg L−1 and stability over a broad pH and temperature conditions. Cybersan showed appreciable growth inhibition toward the clinical bacterial pathogens and revealed no considerable cytotoxicity against the mammalian 3T3 fibroblast cells suggesting its biocompatible nature. This is the first report on a new biosurfactant from a marine yeast having diverse functional properties and evidenced as promising candidate for mammalian safe antimicrobial therapy and other biomedical applications.

Microbes possess a vast reservoir of bioactive compounds, including cyclic lipopeptides (CLPs). In the present study, an exopolymeric biosurfactant composed of lipoheptapeptides was isolated and identified from a marine algicolous bacterial isolate, Bacillus atrophaeus strain AKLSR1, endophytic to Padina tetrastromatica. The lipopeptides were characterized by using FT-IR, NMR, GC–MS and UPLC-ESI-Q-Tof-MS/MS spectroscopic studies. Structural analysis unveiled five CLP variants that formed one major polymeric lipopeptide. These cyclic lipoheptapeptides represent a new class of surfactin family, with significant variations in the fatty acid chain length and amino acid substitutions in the peptide moiety as compared to standard lipopeptides of surfactin family. The critical micelle concentration of this biosurfactant is 0.9 mg L−1 at a surface tension of 28 mN m−1. Polymeric biosurfactant showed stable emulsification index against various organic solvents and vegetable oils. CLPs showed substantial mortality of different cancer cell lines but no toxicity towards normal human lung cell line, MRC5. Further, mechanistic studies revealed cell cycle arrest, ROS accumulation, nuclear fragmentation and cell death. Our studies indicated that CLPs induced apoptosis in lung carcinoma cell line, A549. Anti-proliferative effect of CLPs produced by marine algicolous B. atrophaeus strain AKLSR1 suggests that it could be further explored for biomedical applications.

In recent years, indole-indazolyl hydrazide-hydrazone derivatives with strong cell growth inhibition and apoptosis induction characteristics are being strongly screened for their cancer chemo-preventive potential. In the present study, N-methyl and N,N-dimethyl bis(indolyl)hydrazide-hydrazone analog derivatives were designed, synthesized and allowed to evaluate for their anti-proliferative and apoptosis induction potential against cervical (HeLa), breast (MCF-7 and MDA-MB-231) and lung (A549) cancer cell lines relative to normal HEK293 cells. The MTT assay in conjunction with mitochondrial potential assays and the trypan blue dye exclusion were employed to ascertain the effects of the derivatives on the cancer cells. Further, mechanistic studies were conducted on compound 14a to understand the biochemical mechanisms and functional interactions with various signaling pathways triggered in HeLa and MCF-7 cells. Compound 14a induced apoptosis via caspase independent pathway through the participation of mitogen-activated protein kinases (MAPK) such as extracellular signal related kinase (ERK) and p38 as well as p53 pathways. It originates the activation of pro-apoptotic proteins such as Bak and Mcl-1s and also strongly induced the generation of reactive oxygen species. In downstream signaling pathway, activated p53 protein interacted with MAPK pathways, including SAPK/c-Jun N-terminal protein kinase (JNK), p38 and ERK kinases resulting in apoptotic cell death. The involvement of MAPK cascades such as p38, ERK and p38 on compound 14a induced apoptotic cell death was evidenced by the fact that the inclusion of specific inhibitors of p38, ERK1/2 and JNK MAPK (SB2035809, PD98059 and SP600125) prevented the compound 14a towards induced apoptosis. The results clearly showed that MAP kinase cascades were crucial for apoptotic response in compound 14a induced cellular killing and were dependent on p53 activity. Based on the results, compound 14a was identified as a promising candidate for cancer therapeutics and these findings furnish a basis for further in vivo experiments on anti-proliferative activity.

In an attempt to develop potent and selective anticancer agents, a series of 15 conjugates of 1,4-dihydroindeno[1,2-c]pyrazole chalcone (12a-o) were designed, synthesized and evaluated for their antiproliferative activity against MCF7, A549, MDA-MB-231, HCT116 and SKBR3 human cancer cell lines. Among them, 12h, 12l and 12m showed IC50 values: 3.82, 5.33 and 4.21 μM, respectively, on A549 cell with respect to the positive control, Erlotinib (IC50 value: 10.26 μM). Detailed biological assays showed accumulation of mitotic cells in G2/M phase. In addition, Western blot analysis and immunofluorescence study revealed inhibition of EGFR and Akt pathways. In silico computational studies were also carried out to predict the binding modes and pharmacokinetic parameters of these conjugates.

Glycolipids are ubiquitous and biologically important molecules and are involved in diverse biological functions and exhibit biosurfactant applications due to their surface-active and biodegradability properties. Despite showing a wide range of biological functions, not enough commercial exploitation has been taken place. Possible reasons for this could be the lack of focus or commercially viable processes for isolation/purification, as these glycolipids are found to be complex mixtures in their respective natural sources. Keeping these complexities in view, in this review, we focused on natural occurrences, including plants, marine micro algae, microorganisms, and salient features of various chemical methods, including glycosylation methods for the synthesis of different types of glycolipids. Further, this review significantly summarises the biological evaluation of a diverse class of glycolipids isolated and/or synthesized either by partial or total synthesis.

The compound 1-O-methyl chrysophanol (OMC) which belongs to a class of hydroxyanthraquinones was isolated from Amycolatopsis thermoflava strain SFMA-103 and studied for their anti-diabetic properties. OMC was evaluated as an anti-diabetic agent based on in silico studies which initially predicted the binding energy with α-amylase (−188.81 KJ mol−1) and with α-glucosidase (70.53 KJ mol−1). Further, these results were validated based on enzyme inhibition assays where OMC demonstrated enzyme inhibitory activity towards α-amylase (IC50 3.4 mg mL−1) and α-glucosidase (IC50 38.49 μg mL−1). To confirm the anti-diabetic activity, in vivo studies (oral dose in Wistar rats) revealed that OMC inhibited significantly the increase in glucose concentration at 100 mg/kg as compared to starch control (p in vitro Chinese Hamster Ovary cells (250, 500, and 1000 µM/mL) and in vivo Swiss albino mice (250, 500, and 1000 mg/kg). In vitro results showed that OMC concentration of up to 250 µM/mL did not elicit significant changes in CAs, MI, and MN counts in CHO cells. Similarly, in mice experiments (i.p. injection), no significant changes in CAs, MI, and MN induction were observed till 500 mg/kg of OMC when compared with chrysophanic acid (Cy) (200 mg/kg). In addition, mice that received the lowest dose of OMC (250 mg/kg) did not show any histological changes in liver, kidney, and heart. The study concluded that five times higher therapeutic dose (100 mg/kg) of OMC can be utilized against hyperglycemia with no genotoxic effects.

A new series of triazole-thiazole hybrids were designed, synthesized by the Multi-component reaction approach and evaluated in vitro antimicrobial activity. Most of the tested series of compounds exhibited promising inhibitory activity against the bacterial strains with values in the range of 2.8 to 15.7 µM. The compounds 8i-8l and 8r showed potential-Candida activity against various Candida strains with spectrum values in the range 5.9–14.2 µM. Further, anti-biofilm and toxicity profiles for the potent compounds were also tested, and it was observed that the compounds 8i, 8k, and 8l were found to inhibit the biofilm formation with IC50 values of 6.6, 16.6 and 15.9 µM, respectively against Bacillus subtilis MTCC 121. Besides, 8k and 8l also displayed promising biofilm formation inhibitory activity towards Staphylococcus aureus MTCC 96 with IC50 values of 13.5 and 12.0 µM respectively. In summary, the activity results has emphasized the compounds 8k and 8l as potential leads for further development of antibacterial, anti-Candida, and anti-biofilm agents.

In this study, synthesis of new N-phenoyl phosphatidylethanolamine derivatives was carried out by the modification of natural egg phosphatidylethanolamine (PE) with various phenolic acids. All synthesized products were characterized by NMR, FT-IR and ESI-MS spectral analysis and were evaluated for their preliminary in vitro antioxidant and cytotoxic activities. Among the active derivatives, compounds N-4-hydroxy-3-methoxy cinnamoyl PE, N-4-hydroxy-3,5-dimethoxy cinnamoyl PE and N-(3,4)-di hydroxy cinnamoyl PE were exhibited excellent radical scavenging activity with EC50 values of 9.7, 1.5 and 2.7 µg/mL, respectively which were lower than the standard BHT and α-tocopherols. The synthesized compounds exhibited moderate to very good anticancer activity against four cancer cell lines such as HeLa, B16-F10, SKOV3 and MCF-7 using doxorubicin as a positive control. All the synthesized derivatives may have potential applications in food emulsions and the presence of phenolics has to be examined for additional antioxidant and biological activities.

Herein, we have designed and synthesized new imidazo[2,1-b]thiazole-based aryl hydrazones (9a–w) and evaluated their anti-proliferative potential against a panel of human cancer cell lines. Among the synthesized compounds, 9i and 9m elicited promising cytotoxicity against the breast cancer cell line MDA-MB-231 with IC(50) values of 1.65 and 1.12 μM, respectively. Cell cycle analysis revealed that 9i and 9m significantly arrest MDA-MB-231 cells in the G0/G1 phase. In addition, detailed biological studies such as annexin V-FITC/propidium iodide, DCFH-DA, JC-1 and DAPI staining assays revealed that 9i and 9m triggered apoptosis in MDA-MB-213 cells. Overall, the current work demonstrated the cytotoxicity and apoptosis-inducing potential of 9i and 9m in breast cancer cells and suggested that they could be explored as promising antiproliferative leads in the future.

The compound 1-O-methyl chrysophanol (OMC) which belongs to a class of hydroxyanthraquinones was isolated from Amycolatopsis thermoflava strain SFMA-103 and studied for their anti-diabetic properti...

A series of new 1,4-dihydroindeno[1,2-c]pyrazole tethered carbohydrazide hybrids (5a–u) were designed, synthesized and evaluated for their antimicrobial activity. Compounds 5d, 5g, 5j, 5k and 5q demonstrated significant activity against the entire panel of test pathogens. Further, compounds 5d and 5g exhibited significant anti-Candida activity. These potential hybrids (5d and 5g) also exhibited promising ergosterol biosynthesis inhibition against Candida albicans, which was further validated through molecular docking studies. Furthermore, compounds 5d and 5g caused intracellular ROS accumulation in C. albicans MTCC 3017 and were non-toxic to normal human lung cell line MRC5. In silico studies revealed that they demonstrated drug likeness and an appreciable pharmacokinetic profile. Overall, the findings demonstrate that 5d and 5g may be considered as promising leads for further development of new antifungal drugs.

Ascomycete fungi are promising biofactories producing bioactive compounds exhibiting diverse biological activities. In an ongoing search for bioactive potential of microorganisms from different ecological niches, a promising Lasiodiplodia sp. strain B2 (MTCC 6000) was identified as a producer of exopolysaccharide (designated as Lasiosan). The exopolysaccharide was purified and structurally characterized as glucomannan having glucose and mannose residues (ratio 1:1) with average molecular mass of 29.3 kDa. Lasiosan demonstrated promising antimicrobial and anti-biofilm activities by inhibiting the growth of different Gram-negative, Gram-positive, drug-resistant bacteria and different Candida strains. The purified exopolysaccharide exhibited potential antioxidant activity in terms of good reducing power and scavenging of DPPH free radicals, superoxide anions and lipid peroxyl radicals. Further, the in vitro immune responses of Lasiosan were demonstrated in mouse RAW 264.7 macrophages. Lasiosan inhibited the LPS-stimulated reactive oxygen species (ROS) and nitric oxide (NO) generation in RAW 264.7 macrophages without affecting cell proliferation. Furthermore, Lasiosan significantly down-regulated the production of LPS stimulated proinflammatory mediators such as TNF-α and IL-6 from RAW 264.7 macrophages. This is the first report on Lasiosan exhibiting broad spectrum antimicrobial, anti-biofilm, antioxidant and immunomodulatory activities, which could be explored as a promising candidate for application in biotechnological and biomedical fields.

A series of piperazinyl-1,2-dihydroquinoline carboxylates were synthesized by the reaction of ethyl 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylates with various piperazines and their structures were confirmed by 1H NMR, 13C NMR, IR and mass spectral analysis. All the synthesized compounds were screened for their in vitro antimicrobial activities. Further, the in silico molecular docking studies of the active compounds was performed to explore the binding interactions between piperazinyl-1,2-dihydroquinoline carboxylate derivatives and the active site of the Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID: 2ZCQ ). The docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds 9b and 10c were identified as promising antimicrobial lead molecules. This study might provide insights to identify new drug candidates that target the S. aureus virulence factor, dehydrosqualene synthase.

A new series of bis indolyl tri keto diazo compounds and 3,5-bis(3′-indolyl) triazinones were designed and synthesized as anticancer agents. Their anticancer activity was screened in vitro towards four different human cancer cell lines like HeLa, MCF-7, MDA-MB-231 and A549 cell lines. Among them, compounds 17a and 17b showed potent cytotoxicity with inhibition (IC50) values of 4.6 and 1.3 µM on Human Cervical cancer cell line, respectively. The in silico simulation studies using ADT 1.5.6 tools revealed unique π–π interactions of indole ring of compound 17b with colchicines active site residue Tyr312 could be a valid reason behind its maximum potency when compared to remaining compounds in responsible of its higher activity.

A series of 1, 4-dihydroindeno-[1,2-c] pyrazole linked oxindole conjugates have been synthesized by using Knoevenagel condensation method and further evaluated for their antiproliferative activity against HeLa, A549 and MDA-MB-231 human cancer cell lines along with HEK-293 (normal human embryonic kidney cells). Among the derivatives, compounds 12a, 12b, and 12d showed excellent cytotoxicity with IC50 values ranging between 1.33 to 4.33 μM. Furthermore, detailed biological assays showed that there was accumulation of mitotic cells in G2/M phase, disruption of microtubule network and increase in the G2/M checkpoint proteins (Cyclin B1 and CDK1). Moreover, compound 12d with IC50 value of 1.33 μM showed significant upregulation of tumor suppressor proteins like p53, p21 and pro-apoptotic Bax. The molecular docking analysis demonstrated that these congeners occupy the colchicine binding pocket of the tubulin.

Actinobacteria are prolific producers of a large number of natural products with diverse biological activities. In the present study, an actinobacterium isolated from sunflower rhizosphere soil sample collected from Medak, Andhra Pradesh, South India was identified as Amycolatopsis thermoflava strain SFMA-103. A pigmented secondary metabolite in culture broth was extracted by using methanol and it was further purified by silica gel column chromatography with methanol-chloroform solvent system. Structural elucidation studies based on UV-visible, 1D and 2D-NMR, FT-IR, and mass spectroscopic analyses confirmed the structure as 1-methoxy-3-methyl-8-hydroxy-anthraquinone. It showed significant in vitro anticancer activity against lung cancer and lymphoblastic leukemia cells with IC50 values of 10.3 and 16.98 μM, respectively. In addition, 1-methoxy-3-methyl-8-hydroxy-anthraquinone showed good free radical scavenging activity by DPPH method with an EC50 of 18.2 μg/ml. It also showed other promising superoxide radical scavenging, nitric oxide radical scavenging and inhibition of lipid peroxidation activities. This is a first report of antiproliferative and antioxidant activities of 1-methoxy-3-methyl-8-hydroxy-anthraquinone isolated from A. thermoflava strain SFMA-103 which may find potential application in biotechnological and pharmaceutical fields.

In the enduring investigation of the bioactive microbes, Pseudomonas aeruginosa strain (referred to as CGK-KS-1 (ICTB-315)), isolated from Chumathang hot spring, Ladakh, and India, was identified to possess a major bioactive fraction with antimicrobial and anti-biofilm properties. This bioactive metabolite was purified through bioactivity-guided fractionation. The chemical structure of this major compound was elucidated as phenazine-1-carboxamide (PCN) based on 1H and 13C NMR, FT-IR, EI-HR-MS and 2D NMR spectroscopic techniques. In the current study, PCN exhibited antimicrobial activity with MIC values ranging between 1.9-3.9 μg/ml against various test human pathogens and Xanthomonas spp. PCN showed the antibiofilm property with the IC50 values ranging from 17.04 to 60.7 μM against different test pathogens. The in silico docking studies showed PCN strongly interacted with various proteins of different Xanthomonas spp. with high binding energies. We report herein for the first time the anti-biofilm property and the docking studies of PCN. The extrolite from P. aeruginosa strain CGK-KS-1 showed promising bioactivities and may be considered as a potential candidate for application in various biocontrol strategies.

In galactoceramides, presence of fatty-acyl group on amide moiety or phytosphingosine group is some of the important features that influence the cytotoxicity. Continuous efforts are in progress to modify the fatty-acid moiety and phytosphingosine group present on the galactoceramides to enhance the cytotoxic potential of these compounds. Hence, in the present study, threonine-based β-galactoceramide and its derivatives were prepared by modifying the fatty-acyl group on amide moiety with different fatty-acyl moieties and aromatic acids employing trichloroacetimidate methodology. The structurally related threonine-based ceramide part was synthesized in multi-step process using different reagents. The ceramide part was glycosylated with galactose using trichloroacetimidate as donor. Further, all the synthesized compounds were evaluated for in vitro cytotoxicity against three cancer cell lines and one normal cell line and all the compounds exhibited good to moderate cytotoxicity against all the tested cancer cell lines. In aromatic derivatives, the compound 8i exhibited promising activity against MCF7, A549 and HeLa cancer cell lines with IC50 values of 14.08, 14.78, and 16.70 µM, respectively. In fatty-acid derivatives, two compounds exhibited promising activity, i.e., compound 8m against HeLa with IC50 value 16.34 µM and compound 8n against MCF7 with IC50 value 18.05 µM. Based on structure–activity relationship, aromatic acid derivatives exhibited potential activity as compared to fatty-acid derivatives. Further, the influence of some of the key factors such as spacer chain length between aromatic residue and amide functional group, methoxy substituents on aryl group, terminal unsaturation of fatty acid and branching chain effect on the cytotoxicity are discussed.

A series of novel 2-(trifluoromethyl)-2H/4H-chromene-3-carboxylate isomers 3 and 4 functionalized with diverse methoxybenzenes 2 at position 4 in compound 3 and position 2 in compound 4 were prepared in different proportions by nucleophilic substitution on ethyl 2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate 1 in single step promoted by Indium (III) bromide (5 mol%) a Lewis acid. Regiospecific isomers 3k, 3l, 3m, and 3n prepared by using sterically bulk 1,3,5-trimethoxy benzene substrate 2e in this reaction. Further, isomers 3a and 4a independently on reaction with amines, only compound 3a could give Michael addition products 5a–c. All the compounds 3a–n, 4a–j, and 5a–c were screened for cytotoxic activity against four human cancer cell lines and found to show high activity at micromolar concentration. The compounds 4h and 5a–c showed promising cytotoxic activity against the tested cancer cell lines. Further, these compounds 4h and 5a–c were docked with protein (1SA0) on colchicine-binding site of β tubulin suggesting that tubulin inhibition could be the possible mechanism of action for these compounds.

A series of novel triazolothione, thiadiazole, triazole-functionalized furo/thieno[2,3-b]pyridine derivatives 9a–l, respectively, were prepared starting from 2 (1H) pyridone 3 through selective O/S...

A series of pyran derivatives (5–27) were synthesized in good yields by utilizing Baylis–Hillman chemistry and were further investigated for their in vitro anticancer, antibacterial, and antifungal activities. Most of the tested compounds exhibited promising antibacterial activity as compared to the standard towards Gram-positive bacterial strains. The compounds 5–7, 11–13, and 17–19 displayed two-fold higher activity whereas compound 21 showed four-fold higher antibacterial activity against Staphylococcus aureus MTCC 96 as compared to the standard Neomycin. Some of these compounds exhibited moderate antifungal activity against all the tested fungal strains. Two compounds 16 and 23 showed promising anticancer activity against selected four human cancer cell lines such as A549, DU145, HeLa, and MCF7.

Novel betaines were synthesized from esterquats, which in turn were obtained from the reaction of 11-bromo undecanoic acid, different alkyl amines, and methyl iodide. The synthesized betaines were characterized by fourier transform infrared, proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and mass spectral analysis. These betaines were synthesized in four steps; in the first step, 11-bromo undecanoic acid was converted into methyl 11-bromoundecanoate followed by the synthesis of secondary amine monoester, and tertiary amine mono and diesters by the reaction of 11-bromoundecanoate with different aliphatic amines (hexyl, dodecyl, octadecyl, dioctyl, and dicyclohexyl amine). In the third step, the prepared secondary amine monoesters, tertiary amine mono, and diesters were converted into monoesterquats and diesterquats by reacting with methyl iodide. The resultant esterquats were converted into betaines by saponification reaction using LiOH.H2O in water and tetrahydrofuran. The synthesized compounds (5a–h) were studied for their antimicrobial activity. Some of the compounds showed good to moderate antibacterial activity with minimum inhibitory concentration values ranging between 3.9–31.2 µg mL−1 and antifungal activity with minimum inhibitory concentration values ranging between 7.8–62.4 µg mL−1. Further, some of the betaines also showed good anti-biofilm activity with IC50 values ranging between 2.1–25.3 µg mL−1 on the tested pathogenic microbial and fungal strains.

In the present study, a series of fatty acids-based (short, medium and long unsaturated chains) glycosylated N-fatty acyl-L-tyrosines and N-lipoyl-L-tyrosine methyl esters were synthesized and evaluated for their cytotoxic and antimicrobial activities. The aglycone moiety was synthesized using different chemical reagents. The glycosylation of aglycone moiety with different carbohydrates was performed using the Lewis acid, $$\hbox {BF}_{3.}\hbox {Et}_{2}\hbox {O}$$ . All the synthesized compounds were tested against a panel of four cancer cell lines. The glycosylated N-fatty acyl-L-tyrosines showed moderate activity against all the cell lines and the $$\hbox {IC}_{50}$$ values were in the range of $$15.6{-}45.6\;{\upmu }\hbox {M}$$ . However, the oleic acid analogues (10a, 10d) exhibited $$\hbox {IC}_{50}$$ values of 15.6, $$17.6\;{\upmu }\hbox {M}$$ , respectively, against MDA-MB-231 cell line. Glycosylated N-lipoyl-L-tyrosine methyl esters (6b–6d) showed promising activity against all the tested cell lines and the $$\hbox {IC}_{50}$$ values ranged between $$9.4{-}13.8\;{\upmu }\hbox {M}$$ . The compound 6d exhibited significant cytotoxicity and $$\hbox {IC}_{50}$$ values were 10.5, 9.4, 10.9 and $$12.1\;{\upmu }\hbox {M}$$ against A549, PC3, MDA-MB-231 and HepG2 cell lines, respectively. Moreover, the non-glycosylated N-fatty acyl-L-tyrosine and methyl N-fatty acyl-L-tyrosinate derivatives showed excellent and moderate antimicrobial activity against some of the tested bacterial strains. The glycosylated N-fatty acyl-L-tyrosines with short, medium and long chain unsaturated fatty acids and glycosylated N-lipoyl-L-tyrosine methyl esters were synthesized and further evaluated for their biological activities to examine the impact of sugar and fatty acid on the bioactivity of N-fatty acyl-L-tyrosine derivatives.

Aims The aim of the study was to purify and characterize a bioactive compound from Aspergillus nidulans strain KZR-132 and its biological evaluation. Methods and Results A bioactive extolite was purified from Aspergillus nidulans strain KZR-132, and its chemical structure was elucidated as 3-hydroxylbenzyl alcohol (3-HBA) based on 1H and 13C NMR, FT-IR and mass spectroscopic analysis. The antimicrobial efficacy of 3-HBA was established against Gram-positive, Gram-negative bacteria and different Candida strains. It also showed promising anti-biofilm activity against various tested microbial strains. Reactive oxygen species (ROS) induced by 3-HBA treatment on different Candida strains killed most of the cells and showed necrotic effect. It also exhibited dose-dependent antioxidant and anti-inflammatory activities. Conclusions This bioactive extrolite produced by Aspergillus nidulans isolated from a niche habitat was demonstrated to possess significant biotechnological and pharmacological potential since it exhibited broad spectrum antimicrobial and anti-biofilm activities which are reported for the first time. Significance and Impact of the Study The overall study demonstrates that 3-HBA produced by Aspergillus nidulans KZR-132 is a promising bioactive metabolite and possibly can function as a pharmacologically suitable broad-spectrum antimicrobial drug candidate against various dreaded human-related bacterial and fungal pathogens. This article is protected by copyright. All rights reserved.

Novel N-oxide esters were synthesized from tertiary amine esters, which in turn were obtained from the reaction of 11-bromoundecanoic acid and different alkyl amines. The synthesized N-oxide esters were characterized by fourier transform infrared, proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and mass spectral analysis. The synthetic route involved three steps; initially, 11-bromoundecanoic acid was converted into methyl 11-bromoundecanoate, which was further converted into tertiary amine (mono and di) esters by reacting with different aliphatic amines (hexyl, dodecyl, octadecyl, dioctyl, and dicyclohexyl amine). Finally, the obtained amine esters were converted into N-oxide esters by treating with m-chloroperbenzoic acid. The synthesized N-oxide esters (4a–e) were studied for their antimicrobial and anti-biofilm activities. Among all the synthesized N-oxide esters, compounds 4a and e showed good antimicrobial activity especially towards pathogenic gram-positive bacterial strains with minimum inhibitory concentration values in the range of 7.8–31.2 μg mL−1. The compounds which exhibited antimicrobial activity were also effective in anti-biofilm activity and it was found that the compound 4e exhibited promising biofilm inhibitory activity with IC50 value of 6.4 μg mL−1 against Bacillus subtilis MTCC 121. Further, compound 4e showed increased levels of intracellular reactive oxygen species accumulation, which may be contributing to the bactericidal activity in B. subtilis MTCC 121.

Novel phenoylated phosphatidylcholines were synthesized from 1,2-dipalmitoyl phosphatidylcholine/egg 1,2-diacyl phosphatidylcholine and phenolic acids such as ferulic, sinapic, vanillic and syringic acids. The structures of phenoylated phosphatidylcholines were confirmed by spectral analysis. 2-acyl-1-lyso phosphatidylcholine was synthesized from phosphatidylcholine via regioselective enzymatic hydrolysis and was reacted with hydroxyl protected phenolic acids to produce corresponding phenoylated phosphatidylcholines in 48-56% yields. Deprotection of protected phenoylated phosphatidylcholines resulted in phenoylated phosphatidylcholines in 87-94% yields. The prepared compounds were evaluated for their preliminary in vitro antimicrobial and antioxidant activities. Among the active derivatives, compound 1-(4-hydroxy-3,5-dimethoxy) cinnamoyl-2-acyl-sn-glycero-3-phosphocholine exhibited excellent antioxidant activity with EC50 value of 16.43μg/mL. Compounds 1-(4-hydroxy-3-methoxy) cinnamoyl-2-acyl-sn-glycero-3-phosphocholine and 1-(4-hydroxy-3,5-dimethoxy) cinnamoyl-2-palmitoyl-sn-glycero-3-phosphocholine exhibited good antioxidant activity with EC50 values of 36.05 and 33.35μg/mL respectively. Compound 1-(4-hydroxy-3-methoxy) cinnamoyl-2-palmitoyl-sn-glycero-3-phosphocholine exhibited good antibacterial activity against Klebsiella planticola with MIC of 15.6μg/mL and compound 1-(4-hydroxy-3-methoxy) benzoyl-2-acyl-sn-glycero-3-phosphocholine exhibited good antifungal activity against Candida albicans with MIC of 15.6μg/mL.

A new hybrid template has been designed by integrating the structural features of nimesulide and the 1,2,3-triazole moiety in a single molecular entity at the same time eliminating the problematic nitro group of nimesulide. The template has been used for the generation of a library of molecules as potential anticancer agents. A mild and greener CuAAC approach has been used to synthesize these compounds via the reaction of 4-azido derivative of nimesulide and terminal alkynes in water. Three of these compounds showed promising growth inhibition (IC 50 ∼6–10 μM) of A549, HepG2, HeLa and DU145 cancer cell lines but no significant effects on HEK293 cell line. They also inhibited PDE4B in vitro (60–70% at 10 μM) that was supported by the docking studies (PLP score 87–94) in silico .

Fructooligosaccharides (FOS) are polymers having fructose units with β-glycosidic linkages and a terminal sucrose residue at the reducing end of the oligosaccharides. Due to their non-digestible property, FOS function as prebiotics. In addition, FOS exhibit several therapeutic properties including anti-proliferative, immunomodulatory, and anti-diabetic activities. Inulin is a non-structural polysaccharide abundantly available in various plants. In view of the increasing demand for FOS with prebiotic properties, a renewed interest has engendered researchers to discover microbes producing inulinase and develop bioprocesses based on enzymatic bioconversion of raw inulin for generation of FOS and high-fructose syrup (HFS). This chapter provides an overview of some aspects of microbial inulinase production through fermentation, enzyme immobilization, and purification of FOS. Various fermentation processes for the production of inulinase from different fungal strains are reviewed along with the main substrates and conditions favoring microbial inulinases including physico-chemical parameters. The functional properties and applications of fructooligosaccharides in various systems are also delineated.

Fungal members in the family Botryosphaeriaceae (genus: Lasiodiplodia; teleomorph stage: Botryosphaeria) exhibit diverse ecological and cosmopolitan distribution by infecting a broad range of host plants of both tropical and subtropical biotopes. Botryosphaeriaceae harbors as an endophyte within seeds and other living tissues or survives as a soil-borne saprophyte or as a latent stress-induced pathogen causing dieback, blight, leaf spots, fruit and root rots, gummosis, and canker diseases in perennial fruit and nut trees, vegetable crops, and ornamental plants. The dynamism of these pathogens is evident based on their ubiquitous presence in a broad range of niches and host plants, suggesting their functional role to produce diverse hydrolytic and oxidative enzymes which are of biotechnological and industrial relevance. This chapter also focuses attention on the repertoire of chemically and structurally diverse secondary metabolites, which include small bioactive molecules, taxol/paclitaxel, exopolysaccharides (EPS), etc. A number of case studies on different metabolites produced by different members of genus Lasiodiplodia that find application in medicine, food industry, agriculture, etc. are also presented.