Antimalarial activity and synthesis of new trisubstituted pyrimidines

A series of 2,4,6-trisubstituted-pyrimidines was synthesized and evaluated for their in vitro antimalarial activity against Plasmodium falciparum. Out of the 30 compounds synthesized 21 compounds showed MIC in the range of 0.5-2 microg/mL. These compounds are in vitro several folds more active than pyrimethamine.     

Synthesis of 4-pyrido-6-aryl-2-substituted amino pyrimidines as a new class of antimalarial agents

A series of 2,4,6-trisubstituted pyrimidines were synthesized and evaluated for their in vitro antimalarial activity against Plasmodium falciparum. Of the 18 compounds synthesized, 14 compounds showed MIC in the range of 0.25-2 microg/mL. These compounds are in vitro several fold more active than pyrimethamine.     

Syntheses of 2,4,6-trisubstituted triazines as antimalarial agents

A series of 2,4,6-trisubstituted-1,3,5-triazines (2a-s) were synthesized and evaluated for their in vitro antimalarial activity against P. falciparum. Out of the 19 compounds synthesized eight compounds showed MIC in the range of 1-2 microg/mL. These compounds are in vitro several times more active than cycloguanil.     

Antimalarial activity of 2,4,6-trisubstituted pyrimidines

A series of 2,4,6-trisubstituted pyrimidines (3a-o) was synthesized and evaluated for their in vitro antimalarial activity against P. falciparum. Out of the 15 compounds synthesized 11 compounds showed MIC in the range of 0.5-2 microg/mL. These compounds are in vitro several folds more active than pyrimethamine.     

Synthesis of 2,4,6-trisubstituted pyrimidines as antimalarial agents

A series of 2,4,6-trisubstituted-pyrimidines were synthesized and evaluated for their in vitro antimalarial activity against Plasmodium falciparum. Of the 18 compounds synthesized, 14 compounds have shown MIC in the range of 0.25-2 microg/mL. These compounds are in vitro severalfold more active than pyrimethamine.     

Structure-based de novo design, synthesis, and biological evaluation of the indole-based PPARgamma ligands (I)

MCSS and LeapFrog, two de novo drug design programs, were used for the novel indole-based PPARgamma ligands' study. The designed compounds were synthesized and tested for the PPARgamma protein binding activities in vitro. Out of the compounds that were synthesized, two molecules (compounds 14d and 7d) possessed potent PPARgamma protein binding activity close to rosiglitazone in vitro.     

Solid support synthesis of 6-aryl-2-substituted pyrimidin-4-yl phenols as anti-infective agents

A library of 30 trisubstituted pyrimidines were synthesized and evaluated for their in vitro antimalarial and antitubercular activity. Out of the 30 compounds synthesized, 23 compounds have shown in vitro antimalarial activity against Plasmodium falciparum in the range of 0.25-2 microg/mL and 16 compounds have shown antitubercular activity against Mycobacterium tuberculosis H37Ra, at a concentration of 25 microg/mL.     

Synthesis and pharmacological evaluation of a novel series of 3-aryl-2-(2-substituted-4-methylthiazole-5-yl)thiazolidin-4-one as possible anti-inflammatory and antimicrobial agents

A new series of 3-aryl-2-(2-aryl/benzyl-4-methylthiazole-5-yl)thiazolidin-4-one was synthesized by condensation of 2-aryl/benzyl-4-methylthiazole-5-carbaldehyde, aromatic amines and thioglycolic acid in toluene. All the synthesized compounds are characterized by IR, NMR and elemental or mass analysis. Sixteen out of the newly synthesized compounds were screened for in vivo anti-inflammatory activity using carrageenan-induced rat paw edema method. Some of the synthesized compounds exhibited good anti-inflammatory activity compared with indomethacin. The synthesized compounds were also evaluated for their in vitro antimicrobial activity. Some of the compounds showed mild antibacterial activity while most of the compounds showed good antifungal activity.     

Design, synthesis, synergistic antimicrobial activity and cytotoxicity of 4-aryl substituted 3,4-dihydropyrimidinones of curcumin

3,4-Dihydropyrimidinones of curcumin were synthesized in excellent yield by multi-component one-pot condensation of curcumin, substituted aromatic aldehydes and urea/thiourea under solvent free conditions using SnCl(2)·2H(2)O catalyst. All the synthesized compounds have been characterized by IR, (1)H NMR, (13)C NMR, Mass spectra as well as elemental analyses. The synthesized compounds 4a-n were evaluated for their synergistic antimicrobial (antibacterial and antifungal) activity against bacteria and fungi. Zone of inhibition was measured by adopting disc diffusion method. In vitro minimum inhibitory concentrations were measured using broth microdilution and food poisoning method. In addition to this in vitro cytotoxicity of synthesized compounds against three human cancer lines Hep-G2, HCT-116 and QG-56 were also evaluated. Most of the compounds showed interesting antimicrobial and cytotoxic activity as compared to curcumin, that is, the compounds derived from 2-hydroxy benzaldehyde, 4-hydroxy benzaldehyde and 4-hydroxy-3-methoxy benzaldehyde showed the highest biological activity as compared to other compounds.     

Synthesis and in vitro leishmanicidal activity of some hydrazides and their analogues

Twenty-one hydrazides were synthesized by treating different esters with hydrazine hydrate. Substituted hydrazides were obtained by treating hydrazides with alkyl/aryl/acyl halides. Some of these compounds exhibit potential in vitro leishmanicidal activity. The structures of all the synthesized compounds were confirmed by spectroscopic analysis.     

Synthesis and cytotoxic activity of novel quinazolino-beta-carboline-5-one derivatives

A novel series of quinazolino-beta-carbolinone derivatives was synthesized and evaluated for their in vitro and in vivo anticancer activity. Many compounds have shown good in vitro activity in the range 1-8 microM concentration. Three of the compounds were further tested in nude mice bearing HT-29 colon cancer xenografts.     

One pot synthesis and anticancer activity of dimeric phloroglucinols

A series of dimeric phloroglucinol compounds were synthesized in a single step using commercially available phloroglucinol and methanesulfonic acid. Based on the reported anticancer activity of plant derived dimeric phloroglucinols, these synthesized compounds were evaluated for their in vitro anti-proliferative activities against various cancer cell lines. Several compounds demonstrated in vitro cytotoxic effects across a wide array of tumor cell types. The compound 29 with pyridin-3-yl group on linker methylene and two diisovaleryl phloroglucinol moieties was found to be the most active in all the five cancer cell lines having a low IC(50) of 5.5 μM in colon cancer cell lines (HCT116).     

Anti-malarial activity of Baylis-Hillman adducts from substituted 2-chloronicotinaldehydes

New Baylis–Hillman adducts are synthesized based on substituted 2-chloronicotinaldehydes and screened for their in vitro anti-malarial activity against chloroquine sensitive and chloroquine resistant Plasmodium falciparum. Out of the six new compounds synthesized and screened, 2b, 2c and 2d compounds showed substantial anti-malarial activity.     

A small library of trisubstituted pyrimidines as antimalarial and antitubercular agents

A small library of 20 trisubstituted pyrimidines were synthesized and evaluated for their in vitro antimalarial and antitubercular activities. Out of the total screened compounds, 16 compounds have shown in vitro antimalarial activity against Plasmodium falciparum in the range of 0.25-2microg/mL and 8 compounds have shown antitubercular activity against Mycobacterium tuberculosis H(37)Ra, at a concentration of 12.5microg/mL.     

Antiplasmodial activity of novel keto-enamine chalcone-chloroquine based hybrid pharmacophores

A series of novel keto-enamine chalcone-chloroquine based hybrids were synthesized following new methodology developed in our laboratory. The synthesized compounds were screened against chloroquine sensitive strain (3D7) of Plasmodium falciparum in an in vitro model. Some of the compounds were showing comparable antimalarial activity at par with chloroquine. Compounds with significant in vitro antimalarial activity were then evaluated for their in vivo efficacy in Swiss mice against Plasmodium yoelii (chloroquine resistant N-67 strain), wherein compounds 25 and 27 each showed an in vivo suppression of 99.9% parasitaemia on day 4. Biochemical studies reveal that inhibition of hemozoin formation is the primary mechanism of action of these analogues.     

Design, synthesis and vasodilative activity of tanshinone IIA derivatives

A new series of tanshinone IIA (DIIA) derivatives were synthesized through the reaction of brominated tanshinone IIA (1-Br DIIA) and aromatic acids in the presence of K(2)CO(3). Twenty compounds were synthesized, and all of them were novel. Vasodilative activities for synthesized compounds were valuated in vitro on the contractile response of vascular thoracic aorta smooth muscle from Wistar rats. The results showed that most compounds exhibited a concentration-dependent inhibition on the contractile response of norepinephrine. Four prepared compounds, 4, 5, 8 and 13 revealed relatively remarkable vasodilative activity.     

Synthesis of new S-derivatives of clubbed triazolyl thiazole as anti-Mycobacterium tuberculosis agents

In the present study, a series of N-{4-[(4-amino-5-sulfanyl-4H-1,2,4-triazol-3-yl)methyl]-1,3-thiazol-2-yl}-2-substituted-amide (1a-d) derivatives were synthesized in good yields and characterized by IR, 1H NMR, mass spectral and elemental analyses. The compounds were evaluated for their preliminary in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhosa and then were screened for antitubercular activity against Mycobacterium tuberculosis H37 Rv strain by broth microdilution assay method. The antibacterial data of the tested compounds indicated that most of the synthesized compounds showed better activity against bacteria compared to reference drugs. The in vitro antitubercular activity reports of tested compounds against M. tuberculosis strain H37 Rv showed moderate to better activity.     

Novel coumarin derivatives as potential antidyslipidemic agents

A series of novel benzocoumarin derivatives were synthesized and evaluated for their in vivo antidyslipidemic and in vitro antioxidant activities. Among 11 compounds tested, 2 compounds showed potent antidyslipidemic activity and 3 compounds showed potent antioxidant activity.     

Cinnamic esters of acyclovir-synthesis and biological activity

In the present study we have synthesized esters of acyclovir with cinnamic acids (p-coumaric, ferulic, and sinapic acids) and evaluated them for their antiviral and antioxidant potential. The antiviral activity of the newly synthesized compounds has been tested against human herpes virus 1 (HSV-1) in vitro. The results indicate that none of the synthesized compounds inhibits the tested virus strain. The antioxidant properties have been studied using 2,2-diphenyl-1-picrylhydrazyl (DPPH)* test.