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A simple, efficient and eco-friendly method for the synthesis of 1,2-dihydroquinazolines has been developed using three-component reaction of readily available aromatic aldehydes, 2-aminobenzophenones, ammonium acetate with sulfamic acid as a green and recyclable catalyst. The significant features of this method include short reaction time, operational simplicity, high yields and high selectivity. Interestingly, the catalyst can be recovered and reused for up to four cycles without any loss in catalytic activity. By employing this method, a series of 23 compounds was synthesized and tested for antimicrobial activity against both Gram-positive and Gram-negative bacterial strains as well as a fungal strain. Among these, compounds 4l, 4v and 4w showed appreciable antibacterial activity selectively against Gram-positive bacteria, wherein compound 4w exhibited promising antibacterial activity with MIC value of 0.010 μMol L−1 against Staphylococcus aureus MTCC 96 and Micrococcus luteus MTCC 2470. In addition, 4w also showed promising bactericidal and biofilm formation inhibitory effects. Keywords: 1,2-Dihydroquinazolines, Sulfamic acid, Recyclability, Antimicrobial, Anti-biofilm

Indole/isatin conjugated phenyl-amino-pyrimidine derivatives have been synthesized, characterized and evaluated in vitro for their potential as BCR-ABL inhibitors. Among the series, all derivatives (7a–7o) were found to be more cytotoxic than standard Imatinib against K-562 cell line. Compound 7l was the most active in the series with almost two folds more potency than imitanib (IC50 0.65 μM). In vitro enzymatic studies with recombinant ABL kinase enzyme exhibited promising inhibition in the range of 30–71 µM for most of these novel conjugates. In addition, modelling and other computational studies have been carried out to draw insight into the BCR-ABL protein interactions with the target molecules and drug like properties of the conjugates, respectively.

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.

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...

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.

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.

A series of novel pyrido[2′,3′:3,4] pyrazolo[1,5- a ]pyrimidine derivatives 6 – 9 were prepared in single step starting from 3-amino-6-(trifluoromethyl)-1 H -pyrazolo[3,4- b ]pyridine-5-carboxylate 5 on reaction with symmetrical and unsymmetrical aliphatic and aromatic 1,3-diketones/α,β unsaturated ketones/α,β unsaturated keto ethers under conventional method. All the final compounds 6a – c , 8a – b and 9a – l were screened for anticancer activity against five human cancer cell lines such as PC-3 (CRL-1435), MDA-MB-231 (HTB-26), Hep G2 (HB-8065), HeLa (CCL-2) and normal HUVEC (CRL-1730). Compounds 8a , 9f and 9k which showed promising anticancer activity have been identified. Further, the promising compounds ( 8a and 9f ) were able to inhibit the human topoisomerase I (TopI) activity similar to that of camptothecin.

A series of novel ricinoleic acid based lipoamino acid derivatives were synthesized from (Z)-methyl-12-aminooctadec-9-enoate and different l-amino acids (glycine, alanine, phenyl alanine, valine, leucine, isoleucine, proline and tryptophan). The structures of all the prepared compounds were characterized by 1H NMR, 13C NMR and mass spectral studies. The title compounds were evaluated for their antimicrobial and anti-biofilm activities. Among all the derivatives, compound 7a (Z)-methyl-12-(2-aminoacetamido)octadec-9-enoate exhibited promising antibacterial activity (MIC, 3.9-7.8μg/mL) and compounds 7b (Z)-methyl 12-(2-aminopropanamido)octadec-9-enoate and 7g (Z)-methyl-12-(pyrrolidine-2-carboxamido)octadec-9-enoate exhibited moderate activity (MIC, 7.8-31.2μg/mL) selectively against four different Gram-positive bacterial strains such as Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, S. aureus MLS-16 MTCC 2940, Micrococcus luteus MTCC 2470. These compounds also exhibited excellent antifungal activity against studied fungal strains. Further, the compounds 7a, 7b and 7g were also screened for anti-biofilm activity. Among these lipoamino acid derivatives, compound 7a exhibited good anti-biofilm activity (IC50, 1.9-4.1μg/mL) against four Gram-positive bacterial strains.

An efficient synthesis of thiochromeno[3,4-d]pyrimidine derivatives has been achieved successfully via a one-pot three-component reaction of thiochrome-4-one, aromatic aldehyde and thiourea in the presence of 1-butyl-3-methyl imidazolium hydrogen sulphate [Bmim]HSO4. This new protocol has the advantages of environmental friendliness, high yields, short reaction times, and convenient operation. Furthermore, among all the tested derivatives, compounds 4b and 4c exhibited promising antibacterial, minimum bactericidal concentration and anti-biofilm activities against Staphylococcus aureus MTCC 96, Staphylococcus aureus MLS16 MTCC 2940 and Bacillus subtilis MTCC 121. The compound 4c also showed promising intracellular ROS accumulation in Staphylococcus aureus MLS16 MTCC 2940 comparable to that of ciprofloxacin resulting in apoptotic cell death of the bacterium.

An efficient domino protocol has been developed for the synthesis of new pyrimidine scaffolds, through a one-pot four-component cascade transformation via [Bmim]HSO4 ionic liquid mediated reaction, using an equimolar mixture of thiochroman-4-one, benzaldehyde, thiourea and 3-bromo-1-phenylpropan-1-one leading to the formation of a double electrophilic pyrimidine-2(5H)-thione intermediate. The intermediate regioselectively undergoes cyclization through intramolecular NH bond activation followed by CS bond formation leading to highly functionalized thiazolo[3,2-a]thiochromeno[4,3-d]pyrimidines. The ionic liquid operates efficiently under mild conditions. The recyclability and scope for recovery of the ionic liquid makes this protocol environmentally benign. Further, the compounds 5d, 5g and 5k showed promising antimicrobial activity against the tested Gram-positive bacterial strains. Among them, the compound 5d was identified as a lead molecule exhibiting promising anti-biofilm activity towards Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, Staphylococcus aureus MLS16 MTCC 2940 and Micrococcus luteus MTCC 2470 with IC50 values of 2.1, 1.9, 2.4 and 5.3μg/mL, respectively. Further, the compound 5d showed increased levels of intracellular ROS accumulation in Staphylococcus aureus MTCC 96 suggesting that oxidative stress resulted in bacterial cell lysis and death.

In the present study, Lactobacillus plantarum glycolipid (GL1) molecule in β-configuration and its fatty acid analogues were synthesized using trichloroacetimidate methodology. The β-configuration of the GL1 molecule was unambiguously assigned by NMR studies using 2D-ROESY (NOE) and J-coupling analysis. Dihydrosterculic acid was synthesized using Furukawa's reagent and the selective esterification of dihydrosterculic acid at C-3 position of glycerol was achieved with EDC-HCl at 0 °C. In vitro cytotoxicity of the GL1 molecule and its fatty acid analogues was evaluated against DU145, A549, SKOV3 and MCF7 cell lines. Among all the synthesized molecules, the GL1 molecule and compound 7d showed moderate activity, while the compound 7b showed promising activity against all the tested cell lines with IC50 values of 20.1, 18.2, 19.1 and 17.6 μM, respectively. In addition, all tested compounds showed poor cytotoxicity against normal HUVEC cells. The MCF7 cells when treated with compound 7b showed lower bromodeoxyuridine incorporation levels as compared to untreated cells, suggesting that the compound 7b was highly effective and inhibited the cell proliferation. In addition, the compounds showed significant increase in caspases 3 and 9 levels by inducing apoptosis in MCF 7 cells.

A series of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1,4-dihydro-4-oxoquinoline-3-carboxylate derivatives were prepared through multistep synthesis. The key step in the synthesis was to obtain the C-7 fatty amide derivative. The azide was selectively formed at C-7 position using sodium azide at 60°C. Subsequently, the azide was reduced under mild conditions using zinc and ammonium chloride to form the corresponding amine. The synthesized derivatives were further subjected to biological evaluation studies like cytotoxicity against a panel of cancer cell lines such as DU145, A549, SKOV3, MCF7 and normal lung cells, IMR-90 as well as with antimicrobial and antioxidant activities. It was observed that the carboxylated quinolone derivatives with hexanoic (8a), octanoic (8b), lauric (8d) and myristic (8e) moieties exhibited promising cytotoxicity against all the tested cancer cell lines. The results also suggested that hexanoic acid-based fatty amide carboxylated quinolone derivative (8a) exhibited promising activity against both bacterial and fungal strains and significant antibacterial activity was observed against Staphylococcus aureus MTCC 96 (MIC value of 3.9μg/mL). The compound 8a also showed excellent anti-biofilm activity against Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 121 with MIC values of 2.1 and 4.6μg/mL, respectively.

The total synthesis of sapinofuranones A,B and ent-sapinofuranones A,B and L-factor has been described. A series of novel 1,2,3-triazole-sapinofuranone hybrids were efficiently synthesized employing a click chemistry approach. These sapinofuranones and 1,2,3-triazole-sapinofuranone hybrids were further evaluated for their cytotoxic activity against four human cancer cell lines (A549, MDA-MB-231, DU145 and HepG2). Most of them revealed cytotoxic effects against cancer cells at the micromolar range. From a structure–activity relationship (SAR) perspective, it was noticed that the combination of triazole moiety to the lactone ring is playing modest role in exhibiting the cytotoxic effect. This is the first report on the synthesis and in vitro cytotoxic evaluation of 1,2,3-triazole-sapinofuranone hybrids.

A series of novel trifluoromethyl substituted furo[2,3-b]pyridine and pyrido[3',2':4,5]furo[3,2-d] pyrimidine derivatives 3a-b, 6a-k, 9, 10a-b, 11a-c and 12a-c were prepared from 2-carbethoxy-3-amino-6-trifluoromethyl furo[2,3-b]pyridine 1 under different set of conditions. Compounds functionalized with oxadiazole 11a-c were also prepared from 2-carbohydrazide-3-amino-6-trifluoromethyl furo[2,3-b]pyridine 4. All the final products were screened for anticancer activity against four human cancer cell lines such as Neuro-2a, Hela, A549 and COLO 205 as well as normal human lung cell line, IMR-90. All the compounds showed promising anticancer activity against all the tested cell lines at

A series of novel furo[2,3-b]pyridine-2-carboxamide 4a–h/pyrido[3′,2′:4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives 5a–p were prepared from pyridin 2(1H) one 1 via selective O-alkylation with α-bromoethylester followed by cyclization, then reaction with different aliphatic primary amines to obtain 4 and further reaction with triethyl orthoacetate/triethyl orthoformate. Also prepared novel furo[2,3-b]pyridine-2-carbohydrazide Schiff’s bases 7a–h and pyrido [3′,2′:4,5]furo[3,2-d]pyrimidin-4(3H)-one derivatives 8a–h starting from furo[2,3-b]pyridine carboxylate derivatives 3 by reaction with hydrazine hydrate to form 6 and reaction with diverse substituted aldehydes and cyclization. Products 4a–h, 5a–p, 7a–h and 8a–h were screened against four human cancer cell lines (HeLa, COLO205, Hep G2 and MCF 7) and one normal cell line (HEK 293). Compounds 4e, 4f, 4g, 5h, 7c, 7d, 7e and 7f showed significant anticancer activity against all the cell lines at micro molar concentration and found to be non-toxic to normal cell line. Studies for HeLa, COLO205 and MCF-7 using CoMFA and CoMSIA. Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205 and MCF-7 cell line inhibitors.

BACKGROUND Alkynes are fundamental building blocks in synthetic chemistry with high pharmaceutical applications. Among the bioactive acetylenic molecules, propargylic alcohol is most important as almost all the marketed drugs contains quaternary centered propargylic alcohol functionality. OBJECTIVE In this study we have synthesised and evaluated 3-hydroxy-3-ethynylindolin-2-one derivatives for in vitro cytotoxic activity. METHOD An expeditious method for direct alkynylation of isatins (ketones) has been developed using tetrabutylammonium fluoride (TBAF) as a catalyst in THF solvent at room temperature under metal-free conditions. Furthermore, this method is an economically viable process that also compliments green aspects like being a ligand/metal free process under ambient conditions. This reaction tolerated a wide range of substrates with good to excellent yields (80-94%). RESULTS The results showed that the synthesized compounds (4m, 4n and 4p) has the ability to inhibit Akt kinase activity with IC50 values ranging from 7.7 to 9.8 µM. CONCLUSION All the 3-hydroxy-3-ethynylindolin-2-one derivatives were subjected for in vitro cytotoxic activity on five different cancer cell lines. Further, the synthesized compounds (4m, 4n and 4p) were evaluated for their ability to inhibit Akt kinase activity and exhibited good inhibition with IC50 values ranging from 7.7 to 9.8 µM..

A series of novel pyrido[2,3-d]pyrimidine derivatives 6 were prepared starting from 2-amino-3-cyano-4-trifluoromethyl-6-phenyl pyridine 3 via Grignard’s reaction, cyclization followed by coupling with aliphatic and cyclic amines. All the compounds 6 were screened for antibacterial, minimum bactericidal concentration (MBC), biofilm inhibition activity as well as antifungal and minimum fungicidal concentration (MFC) activities. Among the screened compounds, the compounds 6e, 6f, and 6m which showed exhibiting promising activity have been identified. The results reveal that the compound pyrido[2,3-d]pyrimidine derivative 6e altered the sterol profile which may exert its antifungal activity through inhibition of ergosterol biosynthesis and could be an ideal candidate for antifungal therapy. The molecular docking results also validated the antifungal results.

Fructooligosaccharides (FOS) are gaining tremendous importance as functional food ingredients in view of their multifarious health benefits and pharmaceutical applications. FOS are fructan oligomers available naturally in honey, fruits, and vegetables. FOS are commercially being produced by the transfructosylation of sucrose or hydrolysis of inulin, with the application of enzymes derived from plant and microbial sources. This transfructosylation results in various FOS, such as kestose, nystose, and fructofuranosyl nystose. Inulin hydrolysis results in a similar mixture, although with slightly different end products. These FOS are more soluble in comparison to inulin and are being used as additives in various food products. FOS serves as prebiotics that play a pivotal role in maintaining a healthy gut environment. Low glycemic index, low calorimetric value, increased mineral adsorption are some of the advantages they provide when included in the diet at the appropriate dose. Different fermentation methods employed for the production of FOS and various analytical techniques used for separation and structural elucidation have been discussed in this chapter. In addition, the functional properties and the application of FOS in variety of food formulations and their implications in nutrition and health will be delineated.

An efficient and mild InBr3-catalyzed approach to synthesize 2,3-dihydroquinazolin-4(1H)-one derivatives (3a–3aa) has been developed. Notably, all the products were isolated by recrystallization and the reaction is accessible on a gram scale. Moreover, the reactions only require 10–60 min. All the synthesized compounds were evaluated for their in vitro anticancer activity against four human cancer cell lines.

A number of 3-hydroxy-6-(hydroxymethyl)-2-(2-phenyl-4H-chromen-4-yl)-4H-pyran-4-ones (3) have been synthesized in a one pot catalyst free reaction of 2-hydroxy chalcone (1) with kojic acid (2) in toluene at reflux temperature and evaluated for antimicrobial and anti-biofilm activities. Compounds 3a, 3e, 3f, 3l showed potent antimicrobial activity against Staphylococcus aureus MLS-16 MTCC 2940, Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739, whereas 3b and 3k exhibited excellent activity against Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739, while 3g showed promising activity against Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739. On the other hand, compounds 3a, 3b and 3l showed very good anti-biofilm activity and 3g showed moderate activity against Bacillus subtilis MTCC 121. Whereas, compounds 3a and 3f showed moderate activity against Escherichia coli MTCC 739, while compounds 3a, 3b, 3k and 3l displayed similar activity against Staphylococcus aureus MLS-16 MTCC 2940.

Synthesized sodium N-pamitoyl amino acids were evaluated for surface and antimicrobial properties and compared with sodium lauryl sulfate (SLS). Emulsion stability of the amino acid surfactants and calcium tolerance of the sodium N-palmitoyl isoleucine were better as compared to SLS. Wetting ability and foaming properties of the palmitic acid-based surfactants were inferior to SLS. N-Acyl amino acids exhibited better antibacterial activity compared to sodium salts of N-acyl amino acids and standard compounds against Staphylococcus aureus MLS-16 and Bacillus subtilis. These studies revealed that the palmitoyl amino acid surfactants can be exploited in household, skin care formulations, and industrial applications.

An efficient palladium(0)-catalyzed direct hetero-arylation of imidazo[1,2-a]pyridines at the C-3 position of the imidazole ring has been described. All the synthesized compounds 3a–3r were evaluated for their anticancer activity against a panel of four human cancer cell lines and among all the compounds, 3d, 3j, 3k, 3p and 3r showed promising activity at

2-Styryl quinolines (9a-l) have been synthesized regioselectively from 2-methyl-quinoline by using NaOAc in water acetic acid binary solvents and evaluated for their antibacterial activity against both Gram-positive and Gram-negative strains. Among these, the compounds 12 and 8 were found to be active against both bacterial strains. Compounds 9b, 9f, 9g, 9i, 9j and 9k were the most active among the series exhibiting MIC values ranging between 1.9 and 31.2 μg ml(-1) against different bacterial strains. Compounds 9j and 9k were found to be as potent as the standard drug ciprofloxacin against Micrococcus luteus, Klebsiella planticola and Staphylococcus aureus. In addition, the compounds showed bactericidal activity; compound 9j was found to be better than ciprofloxacin, with an MBC value of 0.9 μg ml(-1) against both M. luteus and K. planticola. The compounds also inhibited biofilm formation, and compound 9j was found to be equipotent to erythromycin against M. luteus and S. aureus MLS16. Further, theoretical studies such as those on druggable properties and PMI plot have been carried out.

Limitations in conventional chemotherapy have resulted in efforts to develop a good drug delivery system for the treatment of several diseases. Many promising drugs that were identified failed to reach the market due to associated drug delivery problems. The ultimate aim of drug delivery systems is to tailor-make the drug formulation to meet the individual requirements under the control of pathophysiological or in vivo conditions, rather than the in vitro characteristics. However, a challenge remains to develop cost-effective, better, and safer nanomaterials for efficient drug loading and controlled drug release. In the recent past, several nanomaterials have been identified with appreciable biocompatibility and therapeutic properties. This chapter focuses on the subject of nanomaterials with regard to their synthetic routes and application as potential drug delivery agents. Different nanomaterial types, including polymeric nanomaterials, dendrimers, nanoparticles, carbon nanotubes, and quantum dots, have been discussed and a number of case studies have been presented.

Apocynin (4-hydroxy-3-methoxy acetophenone), a well known phytochemical, was converted to its oxime and further esterified with fatty acids of different chain lengths (C4-C18) to obtain the oxime esters in about 80% yields. The structures of the oxime esters were confirmed using NMR, IR and mass spectroscopy. The prepared oxime esters of fatty acids and apocynin were evaluated for their in vitro antimicrobial and antioxidant activities. It was observed that the oxime ester of undecenoic acid was the most active apocynin oxime ester that exhibited both antibacterial and antifungal activities. From a mechanistic perspective, it was found that the oxime ester of undecenoic acid acted as an ergosterol biosynthesis inhibitor, confirming its antifungal property. All the compounds exhibited moderate antioxidant activity based on different assays such as DPPH radical scavenging, superoxide free radical scavenging and inhibition of lipid peroxidation. Practical application: The fatty oxime ester could be promising as novel antifungal agent, in view of the increasing resistance of pathogenic fungi to antifungal agents. Oxime esters of apocynin.

Pinolide, a naturally occurring nonenolide and its C2 epimer have been synthesized using d -mannitol and 1,2-epoxyhex-5-ene as the starting materials. The synthesis involves the Jacobsen’s hydrolytic kinetic resolution, Yamaguchi esterification, and intramolecular ring-closing metathesis as the key steps. The 2- epi -pinolide, the C2 epimer of pinolide, has been synthesized for the first time. The cytotoxic activity of the pinolide and 2- epi -pinolide has been studied.

A novel library of Schiff base analogues (5a-q) were synthesized by the condensation of methyl-12-aminooctadec-9-enoate and different substituted aromatic aldehydes. The synthesized compounds were thoroughly characterized by spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, ESI-MS and HRMS). The Schiff base analogues with different substitutions were screened for in vitro antibacterial activity against 7 different bacterial strains. Among these, the compounds with electron withdrawing substituent, namely chlorine (5a) and electron donating substituents, namely hydroxy (5 n) and methoxy (5 o), were found to exhibit excellent to good antimicrobial activities (MIC value 9-18 μM) against Staphylococcus aureus MTCC 96, Staphylococcus aureus MLS-16 MTCC 2940 and Bacillus subtilis MTCC 121. The products were also screened for anti-biofilm and MBC (Minimum Bactericidal Concentration) activities which exhibited promising activities.

A library of diversely stereo-oriented, highly substituted 2,6-cis piperidine derivatives were synthesized, and evaluated for their anticancer activity in cancer cells that included A549 (lung cancer, CCL-185), MCF7 (breast cancer (HTB-22), DU145 (prostate cancer (HTB-81), and HeLa (cervical cancer, CCL-2). One stereo-variant emerged as a promising candidate for further design based structure-activity studies.

A series of new N-alkyl-2-(3-methyl-indolyl)benzimidazoles 8(a–c) were synthesized by the condensation of N-alkyl-2-propylbenzimidazole-phenylhydrazone derivatives 7(a–c), in polyphosphoric acid (PPA) underwent cyclization via Fischer-indole synthesis. Alkylation of 8(b–c) with different alkylating agents gave the title compounds 9(a–f). All the synthesized compounds were characterized by spectral data. The newly synthesized compounds 8(a–c) and 9(a–f) which possess a variety of N-substituents in both benzimidazole and indole moieties, were evaluated for their antimicrobial and anticancer activities. The results showed that compounds 9b, 9c, and 9d were active only against Gram-positive bacteria, and selective antibacterial activity was exhibited by compounds 8c and 8e against Staphylococcus aureus MLS-16 and Bacillus subtilis, respectively. Further, compounds 8a, 8b, 8c, 9a, 9e, and 9f showed significant anti-proliferative activity.

This study presents the synthesis of 14 new 1,4-disubstituted piperazine derivatives from allyl bromides of Baylis–Hillman adduct and 4,4-disubstituted benzhydryl piperazines. All the synthesized compounds were further screened for in vitro ACE inhibitor and antimicrobial activities. Among the synthesized piperazine derivatives, compound 12h showed moderate ACE inhibitor activity as compared to the standard, angiotensin-converting enzyme inhibitor (Sigma). The kinetic data (Km, Ki and Vmax values) of enzyme inhibition for compound 12h and ACE inhibitor standard were also determined. Similarly, all compounds were screened against different bacterial strains. Compounds 12a, 12b, 12d, 12h and 12i showed excellent to moderate activity against various tested bacterial strains. Compounds 12b and 12i showed broad spectrum of antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, S. aureus MLS 16, Escherichia coli, Bacillus subtilis and Klebsiella planticola, while compounds 12a, 12d and 12i showed promising activity against P. aeruginosa (MIC value of 8.96 μM), S. aureus (MIC value of 42.2 μM) and S. aureus MLS 16 (MIC value of 81.3 μM), respectively. The remaining compounds showed activity at a concentration of >491 μM.

Novel lipoamino acids were prepared with the coupling of sapienic acid [(Z)-6-hexadecenoic acid] with α - amino group of amino acids and the resulting N-sapienoyl amino acids were tested for their cytotoxicity activities against four cancer based cell lines. Initially, sapienic acid was synthesized by the Wittig coupling of triphenylphosphonium bromide salt of 6-bromohexanoic acid and decanal with a Z specific reagent. The prepared sapienic acid was subsequently converted to its acid chloride which was further coupled with amino acids by the Schotten-Baumann reaction to form N-sapienoyl amino acid conjugates. Structural characterization of the prepared N-sapienoyl amino acid derivatives was done by spectral data (IR, mass spectra and NMR). These lipoamino acid derivatives were screened for in vitro cytotoxicity evaluation. Cytotoxicity evaluation against four cancer cell lines showed that N-sapienoyl isoleucine was active against three cell lines whereas other derivatives either showed activity against only one or two cell lines with very moderate activity and two derivatives were observed to be inactive against the tested cell lines.

The total synthesis and cytotoxic evaluation of C-9 epimers of herbarumin-II and its C-2 epimer are described for the first time. The key transformations of the synthesis include Wittig olefination, MacMillan α-hydroxylation, Pinnick oxidation, Yamaguchi esterification, and intramolecular ring closing metathesis.

Novel fatty acid ester derivatives comprising sapienic acid [(Z)-6-hexadecenoic acid] and functional phenolics were synthesized following a chemo-enzymatic approach. Sapienic acid was synthesized by Wittig coupling of triphenylphosphonium bromide salt of 6-bromohexanoic acid and decanal with a cis specific reagent. Sapienic acid was chemo selectively esterified with six phenolic compounds to produce sapienate esters of six phenolics using a lipase in organic solvent medium. Structural characterization of the prepared fatty acid ester derivatives was done by spectral data (IR, mass spectra, and NMR). The sapienic acid ester derivatives were screened for in vitro antioxidant and cytotoxicity evaluation. These derivatives exhibited good radical scavenging activity as determined by the diphenylpicryl hydrazyl (DPPH) radical scavenging assay. Sapienic ester of hydroxytyrosol was found to exhibit highest DPPH radical scavenging activity and was greater than commercial antioxidants. Cytotoxicity evaluation against four cancer cell lines showed that three esters out of six were found to exhibit moderate cytotoxicity with coniferyl derivative being more active than the others against all the tested cell lines.