Amino acid-based enantiomerically pure 3-substituted 1,4-benzodiazepin-2-ones: a new class of anti-ischemic agents

A series of 3-substituted 1,4-benzodiazepin-2-ones derived from S and R amino acids were evaluated for their anti-ischemic activity in vitro. Treatment with compounds 7h, 16, 9d, and 17 decreased the apoptotic neuronal number, however increased the neuronal viability. The compounds decreasing apoptosis could protect neurons from the ischemic injury. The difference in the activities of 1,4-benzodiazepin-2-ones derived from S- and R-amino acids is discussed and explained on the basis of molecular modeling studies.     

5-substituted 2'-fluoro-arabinonucleosides as potential antiviral agents

In order to study the electronic effects of 5-substituents of 2'-fluoro-ara-U on antiviral activity, eight nucleosides were synthesized and screened for their activity. Preliminary in vitro studies revealed that 5-thiocyano-, 5-hydroxy- and 5-formyl-ara-U are moderately active against HSV-1, HSV-2 and VZV, but they are also cytotoxic. None of these showed significant activity against CMV.     

Development of a new class of potential antiatherosclerosis agents: NO-donor antioxidants

A new class of NO-donor phenol derivatives is described. The products were obtained by joining appropriate phenols with either nitrooxy or 3-phenylsulfonylfuroxan-4-yloxy moieties. All the compounds proved to inhibit the ferrous salt/ascorbate induced lipidic peroxidation of membrane lipids of rat hepatocytes. They were also capable of dilating rat aorta strips precontracted with phenylephrine.     

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.     

Novel dihydropyrimidines as a potential new class of antitubercular agents

A small library of 30 dihydropyrimidines was synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H₃₇Rv. Two compounds, ethyl 4-[3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5 carboxylate 4a and ethyl 4-[3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 4d were found to be the most active compounds in vitro with MIC of 0.02 μg/mL against MTB and were more potent than isoniazid.     

Methyl 2-(2-(4-formylphenoxy)acetamido)-2-substituted acetate derivatives: a new class of acetylcholinesterase inhibitors

A new class of inhibitors of acetylcholinesterase (methyl 2-(2-(4-formylphenoxy)acetamido)-2-substituted acetate derivatives) is described. Compounds 4b and 4i were found to be more potent than galanthamine in inhibiting acetylcholinesterase.     

Synthesis and biological evaluation of novel 4-substituted 1-{[4-(10,15,20-triphenylporphyrin-5-yl)phenyl]methylidene}thiosemicarbazides as new class of potential antiprotozoal agents

A novel series of 4-substituted 1-{[4-(10,15,20-triphenylporphyrin-5-yl)phenyl]methylidene}thiosemicarbazide, 4a-4n, was synthesized in 9-21% yield by the condensation of 4-(10,15,20-triphenylporphyrin-5-yl)benzaldehyde (3) with various substituted thiosemicarbazides in presence of catalytic amount of AcOH. These compounds were assayed for in vitro antiamoebic activity, and the results showed that out of 14 compounds 9 were found with IC(50) values lower than metronidazole corresponding to 1.05- to 4.7-fold increase in activity. MTT Assay showed that all the compounds are nontoxic to human kidney epithelial cell line. 4-(m-Toluidinyl)-1-{[4-(10,15,20-triphenylporphyrin-5-yl)phenyl]methylidene}thiosemicarbazide (4h) showed the highest antiamoebic activity with least cytotoxicity. Some of the compounds were screened for their antimalarial activities and ability to inhibit beta-haematin formation, but none of them showed an activity better than chloroquine and quinine. Only one compound out of six showed an activity comparable to standard drug.     

Synthesis of a new class of 2-anilino substituted nicotinyl arylsulfonylhydrazides as potential anticancer and antibacterial agents

A series of N'-1-[2-anilino-3-pyridyl]carbonyl-1-benzenesulfonohydrazide derivatives (7a-i) was synthesized and five of them were selected by the National Cancer Institute (NCI) and evaluated for their in vitro anticancer activity. Three of the investigated compounds 7d, 7f and 7g exhibited significant anticancer activity in the primary assay and further tested against a panel of 60 human tumour cell lines. Compound 7g showed 50% growth inhibitory activity in leukaemia, melanoma, lung cancer, colon cancer, renal cancer and breast cancer cells with GI(50) value of 3.2-9.6 microM. The synthesized compounds (7a-i) were also evaluated for their antibacterial activity against various Gram-positive and Gram-negative strains of bacteria. Most of these compounds showed better inhibitory activity in comparison to the standard drugs.     

Amino acid based enantiomerically pure 3-substituted benzofused heterocycles: A new class of antithrombotic agents

A diverse group of novel medium ring heterocycles derived from naturally abundant proteinogenic amino acids were evaluated for their potency towards antithrombotic activity. The more potent benzofused oxazepine and oxazocine scaffolds were diversified by incorporating different amino acids at the position number 3. Further the effect of ring size has also been taken into account and it was observed that the eight-membered oxazocines ane more potent compared to the corresponding oxazepines.     

(+/-)-2-(3-Piperidyl)-1,2,3,4-tetrahydroisoquinolines as a new class of specific bradycardic agents

A series of (+/-)-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines were prepared and their bradycardic activities were examined in isolated guinea-pigs' right atria and in anesthetized rats. Modifications on the benzyl moiety of the parent compound, 1, led to the identification of compound 11e as a potent and specific bradycardic agent.     

Arylanthranilodinitriles: a new biaryl class of antileishmanial agents

A series of anthranilodinitrile-based biaryls were synthesized and evaluated in vitro against extracellular promastigotes and intracellular amastigotes of Leishmania donovani. Among various screened compounds, a biaryl with trifluoromethyl group 5f showed 83% inhibition against promastigotes and 70% inhibition against amastigotes of L. donovani at 8 and 20microg/mL concentrations, respectively.     

Discovery of isoalloxazine derivatives as a new class of potential anti-Alzheimer agents and their synthesis

This article describes discovery of a novel and new class of cholinesterase inhibitors as potential therapeutics for Alzheimer’s disease. A series of novel isoalloxazine derivatives were synthesized and biologically evaluated for their potential inhibitory outcome for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds exhibited high activity against both the enzymes AChE as well as BuChE. Of the synthesized compounds, the most potent isoalloxazine derivatives (7m and 7q) showed IC₅₀ values of 4.72 μM and 5.22 μM respectively against AChE; and, 6.98 μM and 5.29 μM respectively against BuChE. These two compounds were further evaluated for their anti-aggregatory activity for β-amyloid (Aβ) in presence and absence of AChE by performing Thioflavin-T (ThT) assay and Congo red (CR) binding assay. In order to evaluate cytotoxic profile of these two potential compounds, cell viability assay of SH-SY5Y human neuroblastoma cells was performed. Further, to understand the binding behavior of these two compounds with AChE and BuChE enzymes, docking studies have been reported.     

Synthesis and evaluation of a class of new coumarin triazole derivatives as potential antimicrobial agents

A series of new coumarin-based 1,2,4-triazole derivatives were designed, synthesized and evaluated for their antimicrobial activities in vitro against four Gram-positive bacteria (Staphylococcus aureus, MRSA, Bacillus subtilis and Micrococcus luteus), four Gram-negative bacteria (Escherichia coli, Proteus vulgaris, Salmonella typhi and Shigella dysenteriae) as well as three fungi (Candida albicans, Saccharomyces cerevisiae and Aspergillus fumigatus) by two-fold serial dilution technique. The bioactive assay showed that some synthesized coumarin triazoles displayed comparable or even better antibacterial and antifungal efficacy in comparison with reference drugs Enoxacin, Chloromycin and Fluconazole. Coumarin bis-triazole compounds exhibited stronger antibacterial and antifungal efficiency than their corresponding mono-triazole derivatives.     

Polysubstituted 2H-pyran-2-ones: A new class of hepatoprotective agents

The synthesis and hepatoprotective activity of 6-aryl-3-substituted-4-methylthio-2H-pyran-2-ones (3, 5, 7) and the corresponding 2-thiones (6), 6-aryl-4-methylthio-2H-pyran-2-ones (4) and 6-aryl-3-carbethoxy-5-cyano-4-methylthio-2H-pyran-2-ones are described.     

Synthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatory and analgesic agents

Treatment of 3-cyanoacetyl indole 1 with the diazonium salts of 3-phenyl-5-aminopyrazole and 2-aminobenzimidazole afforded the corresponding hydrazones 4 and 5. 3-Cyanoacetyl indole reacted with phenylisothiocyanate to give the corresponding thioacetanilide derivative 7. Treatment of 7 with hydrazonoyl chlorides afforded the corresponding 1,3,4-thiadiazole derivatives 8a-f and 9. Also, the thioacetanilide reacted with alpha-haloketones to afford thiophene derivatives 10a,b (tenidap analogues), or thiazolidin-4-one derivative 11. The newly synthesized compounds were found to possess potential anti-inflammatory and analgesic activities.     

Design and synthesis of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones as a novel class of analgesic and anti-inflammatory agents

A new series of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(4-ethylphenyl)-3H-quinazolin-4-one from 4-ethyl aniline with a variety of aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. The compound 2-(N'-3-pentylidene-hydrazino)-3-(4-ethylphenyl)-3H-quinazolin-4-one (AS2) emerged as the most active compound of the series and was moderately more potent than the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to aspirin.     

Design and synthesis of 3-(4-Ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones as a novel class of analgesic and anti-inflammatory agents

A new series of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(4-ethylphenyl)-3H-quinazolin-4-one from 4-ethyl aniline with a variety of aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. The compound 2-(N′-3-pentylidene-hydrazino)-3-(4-ethylphenyl)-3H-quinazolin-4-one (AS2) emerged as the most active compound of the series and was moderately more potent than the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to aspirin.     

Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents

Structural derivatives of 4-MTA, an illegal amphetamine analogue have been previously shown to have anticancer effects in vitro. In this study we report the synthesis of a series of novel 1,3-bis(aryl)-2-nitro-1-propene derivatives related in structure to 4-MTA. A number of these compounds containing a classic nitrostyrene structure are shown to have antiproliferative activities in vitro in a range of malignant cell lines, particularly against Burkitt's lymphoma derived cell lines, whilst having no effect on 'normal' peripheral blood mononuclear cells. Such effects appear to be independent of the serotonin transporter, a high affinity target for amphetamines and independent of protein tyrosine phosphatases and tubulin dynamics both of which have been previously associated with nitrostyrene-induced cell death. We demonstrate that a number of these compounds induce caspase activation, PARP cleavage, chromatin condensation and membrane blebbing in a Burkitt's lymphoma derived cell line, consistent with these compounds inducing apoptosis in vitro. Although no specific target has yet been identified for the action of these compounds, the cell death elicited is potent, selective and worthy of further investigation.     

1,2,4-Oxadiazoles: a new class of anti-prostate cancer agents

Sulfide and sulfonyl derivatives of 1,2,4-oxadiazoles were synthesized and screened by MTT assay on the prostate cancer cells, DU-145. Six compounds were identified as potential anti-prostate cancer agents with IC(50) values ranging from 0.5 to 5.1μM. These compounds exhibited good activity on the androgen independent cells PC-3, while the results were moderate on androgen dependent LNCaP cells, suggesting the possibility of a mechanism of action different from that of the bioisosteric bicalutamide. Also a very low cytotoxicity was observed on non-cancerous cells MCF-10A.