Synthesis of novel 1,2,3-thiadizoles and 1,2,3-selenadiazoles as new antimicrobial agents

Abstract

A series of novel 1,2,3-thiadiazoles and 1,2,3-selenadiazoles having a long alkyl chain were synthesized by reacting semicarbazones with SOCl₂ and SeO₂, respectively. The structures of the target compounds 5–12 were confirmed by spectroscopy (IR, ¹H NMR, ¹³C NMR, and MS) and elemental analysis. Their antibacterial and antifungal activities were evaluated against six bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus) and three fungi (Candida albicans, Candida parapsilosis, Candida tropicalis). The results of bioassays indicated that the compounds 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]selenadiazole (7), 4-Methyl-5-tetradecyl-[1-3]selenadiazole (8) and 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]thiadiazole (11) displayed moderate antibacterial activity against S. Epidermidis. On the other hand, according to antifungal screening results, compounds 5-Dodecyl-4-phenyl-[1-3]selenadiazole (5), 4-p-Tolyl-5-undecyl-[1-3]selenadiazole (6), and 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]selenadiazole (7) exhibited significant antifungal activities studied yeast strains.     

Dicationic liquid mediated synthesis of tetrazoloquinolinyl methoxy phenyl 4-thiazolidinones and their antibacterial and antitubercular evaluation

In a search of new potentially active antitubercular agents here we have synthesized 3-substituted phenyl-2-(4-(tetrazolo[1,5-a]quinolin-4-ylmethoxy)phenyl)thiazolidin-4-ones (8a–l) and evaluated their antibacterial, particularly antitubercular activity. These have been conveniently synthesized by performing one–pot cyclocondensation of 4-(tetrazolo[1,5-a]quinolin-4-ylmethoxy)benzaldehyde, anilines and mercaptoacetic acid in dicationic ionic liquid, (3-methyl-1-[3-(methyl-1H-imidazolium-1-yl)propyl]-1H-imidazolium dibromide [C₃(MIM)₂–2Br]) and obtained excellent yields of (8a–l). 4-Thiazolidinones (8a–l) were thoroughly characterized by their spectral analyses. These compounds have been screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra and Mycobacterium bovis (BCG). The compounds 8a, 8c, and 8e exhibited notable in vitro antitubercular activity compare to the reference, Rifampicin. Molecular docking study has also been performed to know the binding mode of these analogs in to the active site of DprE1 enzyme. The synthesized compounds were also evaluated for their in vitro antibacterial activity and amongst them compound 8k has shown moderate activity against both gram-negative and gram-positive bacterial strains.     

Chemical constituents and biological activities of Viburnum macrocephalum f. keteleeri

Three new compounds (1–3) and seven known compounds (4–10) have been isolated from the ethanolic extract of Viburnum macrocephalum f. keteleeri using bioactivity-guided fractionation and identified as methyl (2-α-L-rhamnopyranosyloxy)acetate (1), methyl (2R-3-α-L-rhamnopyranosyloxy)glycerate (2), methyl (3R-4-α-L-rhamnopyranosyloxy-3-hydroxy)butanoate (3), bridelionoside B (4), (6S,7E,9R)-roseoside (5), linarionoside A (6), 3,7,11-trimethyl-1,6-dodecadien-3,10,11-triol (7), (+)-8-hydroxylinalool (8), β-sitosterol (9) and daucosterol (10). The structures of 1–3, including absolute configurations, were determined by spectroscopic data (¹H and ¹³C NMR, HSQC, HMBC and ORD) and chemical methods. In addition, compounds 1–8 were assayed for their insecticidal and antimicrobial activities. Compounds 7 and 8 exhibited moderately insecticidal effects against Mythimna separata with LD₅₀ values of 180 and 230 μg g^?1, respectively. Compounds 2, 3, 7 and 8 showed varying antimicrobial activities with IC₅₀ values ranging from 125 to 529 μM.     

Synthesis and investigation of antibacterial activities and carbonic anhydrase and acetyl cholinesterase inhibition profiles of novel 4,5-dihydropyrazol and pyrazolyl-thiazole derivatives containing methanoisoindol-1,3-dion unit

Novel 4,5-dihydropyrazole derivatives (3a–i), 3-(4-((3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-2(3H)-yl)phenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothio amide, were obtained by the addition of thiosemicarbazide (2) to the chalcones (1a–i). The addition–cyclization of 2,4′-dibromoacetophenone (4) to pyrazole derivatives (3a–i) gave the new pyrazolyl-thiazole derivatives (5a–i), (3aR,4S,7R,7aS)-2-(4-(1-(4-(4-bromophenyl)thiazol-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione. Antibacterial and acetylcholinesterase (AChE) enzyme and human carbonic anhydrase (hCA) I, and II isoform inhibitory activities of the compounds 3a–i and 5a–i were investigated. Some of the compounds showed promising antibacterial activity. In addition, the hCA II and I were effectively inhibited by the lately synthesized derivatives, with K_i values in the range of 18.90?±?2.37 ?58.25?±?13.62?nM for hCA II and 5.72?±?0.98 ?37.67?±?5.54?nM for hCA I. Also, the K_i parameters of these compounds for AChE were obtained in the range of 25.47?±?11.11???255.74?±?82.20?nM. Also, acetazolamide, clinical molecule, was used as a CA standard inhibitor that showed K_i value of 70.55?±?12.30?nM against hCA II, and 67.17?±?9.1?nM against hCA I, and tacrine inhibited AChE showed K_i value of 263.67?±?91.95.     

Synthesis and Anticancer Activity of Novel Nonfused Bicyclic Thiazolidinone Derivatives

A series of new 2-{4-oxo-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]-thiazolidin-5-yl}-N-arylacetamides ( 4a–e ), 5-(2-oxo-2-aryl-ethyl)-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]-thiazolidine-4-ones ( 5a–d ), 2-(4-oxo-2-[(2-oxothiazolidin-4-ylidene)-hydrazono]-thiazolidin-5-yl)-N-arylacetamides ( 7a–e ), and 5-(2-oxo-2-aryl-ethyl)-2-[(2-oxothiazolidin-4-ylidene)-hydrazono]-thiazolidine-4-ones ( 8a–d ) have been synthesized starting from 2-thioxothiazolidin-4-one and 4-thioxothiazolidin-2-one through a multistep reaction sequence. 2-Thioxothiazolidin-4-one was alkylated via the intermediate formation of the triethylammonium salt 1 by ethyl chloroacetate. Compound 2 and 4-thioxothiazolidin-2-one reacted with thiosemicarbazides to give the 1-(4-thiazolidinone-2-ylidene)-4-R-thiosemicarbazones ( 3a,b ) and 1-(2-thiazolidinone-4-ylidene)thiosemicarbazones ( 6a,b ), respectively. Following [2+3]-cyclization of thiazolidinone-substituted thiosemicarbazones ( 3a,b and 6a,b) with N-arylmaleimides and aroylacrylic acids as equivalents of dielectrophilic synthon [C₂]^{2 +}, novel non-fused bicyclic thiazolidinones ( 4a–e, 5a–d, 7a–e, 8a–d ) were synthesized. The structures of the new compounds ( 4a–e, 5a–d, 7a–e, 8a–d ) were established on the basis of their elemental analysis and ¹H NMR and mass spectral data. Eight of the synthesized compounds were tested, and three of them displayed different levels of antitumor activity. The most efficient antitumor agent—2-{4-oxo-3-furylmethyl-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]-thiazolidin-5-yl}-N-4-chlorophenylacetamide ( 4d ) was found to be active against leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancer cell lines with mean lgGI₅₀ and lgTGI values of –5.35 and –4.78, respectively.     

Succinct and Facile Synthesis of Innovative Thiopyrimidines With Antimicrobial and Antitubercular Investigation

Abstract

To develop a series of bioactive heterocycles in minimum number of steps, 3-methyl- 4-(substituted phenyl)-1-phenyl-4,8-dihydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5,7 (1H,6H)-dithione 2(a–j), 4-(4-substituted phenyl)-5-imino-3-methyl-1,6-diphenyl-4,5,6,8-tetrahydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-7(1H)-thione 3(a–j), and N-[4-(subs- tituted phenyl)-3-methyl-1-phenyl-7-thioxo-1,4,7,8-hexahydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5-yl]thiourea 4(a–j) have been synthesized from amino nitrile functionality 1(a–j). The structures of the compounds were elucidated by IR, ¹H NMR, elemental analysis, and some representative ¹³C NMR and mass spectra. All the title compounds were screened for antimicrobial and antitubercular activities, while some representative compounds were tested for antioxidant activity. Out of synthesized compounds, compounds 1j (4-CH₃), 2d (4-F), 4c (4-OH), and 4i (3-Br) exhibited maximum inhibition against Mycobacterium Tuberculosis H₃₇Rv. Compound 3c (4-OH) revealed elevated efficacy against all tested bacterial strain, while compounds 1i (3-Br), 2c (4-OH), and 3h (3-NO₂) were found efficacious against Candida albicans as compared to standard drugs.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Syntheses,crystal structures and antibacterial activities of two new Mn(II) complexes based on triaryltriazoles

Two new Mn(II) complexes, trans-[Mn(L1-L2)₂(NCS)₂] (1–2) with triaryltriazole (1, L1 = 3-(p-bromophenyl)-4-phenyl-5-(2-pyridyl)-1,2,4-triazole; 2, L2 = 3,4-bis(p-methylphenyl)-5-(2-pyridyl)-1,2,4-triazole), have been synthesized and structurally characterized by elemental analysis, FT-IR, ESI-MS, and single-crystal X-ray crystallography. Crystallographic studies revealed that both 1 and 2 contain a distorted octahedral [MnN₆] core with two trans-disposed NCS^? ions. The L1 ligand, 1 and 2, together with four known homologous Mn(II) complexes, trans-[Mn(L3-L6)₂(NCS)₂] (3–6) (3, L3 = 3-(p-methoxyphenyl)-4-(p-chlorophenyl)-5-(2-pyridyl)-1,2,4-triazole; 4, L4 = 3-(p-methoxyphenyl)-4-(p-bromophenyl)-5-(2-pyridyl)-1,2,4-triazole; 5, L5 = 3-(p-chlorophenyl)-4-(p-methylphenyl)-5-(2-pyridyl)-1,2,4-triazole; 6, L6 = 3,5-bis(2-pyridyl)-4-(p-methylphenyl)-1,2,4-triazole), were tested in vitro for their antibacterial activities against two Gram-positive bacterial strains and two Gram-negative bacterial strains by the MTT method. The results indicate that 1 exhibited better activity than Penicillin and Kanamycin against Pseudomonas aeruginosa and also better than its free L1 ligand.     

Synthesis and antiproliferative activities of aminoalkylated polymethoxyflavonoid derivatives

A series of novel aminoalkylated polymethoxyflavonoid derivatives 3–11 was synthesised from 5-hydroxy-3,7,3′,4′-tetramethoxyflavonoid (1) through extending alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at the end of the side chain. Their antiproliferative activities were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3). The results showed that all the target compounds exhibited antiproliferative activities against investigated cancer cells with IC₅₀ values of 9.51–53.33 μM. Compounds 5, 7, 8, 11 on Hela cells and compounds 4–9, 11 on HCC1954 exhibited more potency as compared to positive control cis-Platin.     

Scillapersicene: a new homoisoflavonoid with cytotoxic activity from the bulbs of Scilla persica HAUSSKN

The phytochemical investigation of Scilla persica HAUSSKN bulbs led to the isolation of a novel homoisoflavonoid that named Scillapersicene (1) and identified as 3-(3′,4′-dihydroxybenzylidene)-8-hydroxy-5,7-dimethoxychroman-4-one along with five known homoisoflavonoids 2–6, whose structures were elucidated using HRFAB-MS, 1D and 2D NMR spectroscopic data. The known compounds were identified as 3-(3′,4′-dihydroxybenzyl)-5,8-dihydroxy-7-methoxychroman-4-one (2), 3,9-dihydro-autumnalin (3), autumnalin (4), 3-(3′,4′-dihydroxybenzylidene)-5,8-dihydroxy-7-methoxychroman-4-one (5) and scillapersicone (6). All compounds obtained, expect 2 and 4, showed strong cytotoxic activity against AGS cell line. The toxicity on AGS cell line was measured by 1, 3, 5 and 6 with IC₅₀ values of 8.4, 30.5, 10.7 and 24.2 μM, respectively. In addition, the physico-chemical properties of these natural compounds were optimised using density functional method (B3LYP) with standard 6-311+G* basis set. These natural products have low-energy gaps between the first ionisation potentials and highest occupied molecular orbital. In conclusion, the low-energy gap could cause reason for cytotoxic activity of homoisoflavonoids.     

Cytotoxic tremulanes and 5,6-secotremulanes,four new sesquiterpenoids from a plant-associated fungus X1-2

Two new tremulanes and two new 5,6-secotremulanes, davotremulanes A-D 1–4, along with four known compounds 5–8, were isolated from the culture extract of X1-2, an unidentified plant-associated fungus, which was isolated from the endangered plant, Davidia involucrate Baill. in Shennongjia District. The structures of new compounds 1–4 were established on the basis of extensive spectroscopic analysis. Compounds 1–8 were evaluated for cytotoxic activity to four cancer cell lines, and compounds 1, 2 and 5 displayed selectively moderate activities to A549 cell line with IC₅₀ at 15.3, 25.2, 35.2 μg/mL.     

A new alkaloid from Portulaca oleracea L. and its antiacetylcholinesterase activity

A new alkaloid, (10E, 12E)-9-ureidooctadeca-10, 12-dienoic acid, named oleraurea (1) and 10 known compounds, p-hydroxybenzaldehyde (2), p-hydroxybenzoic acid (3), p-hydroxyacetophenone (4), benzamide (5), (E)-p-coumaramide (6), (E)-ferulamide (7), soyalkaloid A (8), β-carboline-3-carboxylic acid (9), 2, 3, 4, 9-tetrahydro-1H-pyrido [3, 4-b] indole-3-carboxylic acid (10), (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid (11) were obtained from Portulaca oleracea L., in which, compounds 4, 5, 8–11 were isolated from the plant for the first time. The structure of the compound 1 was identified using spectroscopic methods including 1D and 2D NMR, HR-ESI-TOF-MS. The compounds 1, 5–11 presented anticholinesterase activities, but the P. oleracea extract (POE) presented very low anticholinesterase activity.     

Studies on Pyrazine Derivatives,XLV: Synthesis,Reactions, and Tuberculostatic Activity of N-Methyl-N′-(pyrazine-2-carbonyl)-hydrazinecarbodithioic Acid Methyl Ester

Methyldithiocarbonyl derivative 2 of pyrazine-2-carboxylic acid N′-methyl-hydrazide 1 was synthesized by methylation of CS₂ adduct. Benzylamine caused the decomposition of compound 2 to pyrazine-2-carboxylic acid benzylamide 5 and 1,3-dibenzylthiourea 6. N-methyl-N′-(pyrazine-2-carbonyl)-hydrazinecarbodithioic acid methyl ester 2 were evidenced to cyclize to 3-methyl-5-pyrazin-2-yl-3H-[1, 3, 4]oxadiazole-2-thione 8 in the presence of triethylamine. In the reactions with secondary amines such as morpholine, pyrrolidine and phenylpiperazine pyrazinoyl derivatives (9–11) of thiosemicarbazide were obtained. Hydrazine, methylhydrazine, aminoalcohols, and N-alkylamino-substituted cyclic amines reacted with cyclization to 4-substituted 1,2,4-triazole-3-thiones 12, 13, and 18–22. Synthesized compounds exhibited low tuberculostatic activity in vitro (MIC 50–100 μg/mL).     

Hepatoprotective phenylethanoid glycosides from Cirsium setosum

Two new phenylethanoid glycosides, namely β-D-glucopyranoside, 1″-O-(7S)-7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3″-α-L-rhamnopyranosyl-4″-[(8E)-7-(3-methoxyl-4-hydroxyphenyl)-8-propenoate] (1) and β-D-glucopyranoside, 1″-O-(7S)-7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3″-α-L-rhamnopyranosyl-4″-[(8E)-7-(4-hydroxyphenyl)-8-propenoate] (2), together with six phenylethanoid glycosides were isolated from Cirsium setosum. Their structures were elucidated by their spectroscopic data and references. Compounds 2, 4, 5, 7 and 8 (10 μM) exhibited moderate hepatoprotective activities. Compounds (3–8) were obtained from this plant for the first time.     

A new curvularin glycoside and its cytotoxic and antibacterial analogues from marine actinomycete Pseudonocardia sp. HS7

Five curvularin macrolides (1–5) were isolated from the cultured broth of marine actinomycete Pseudonocardia sp. HS7 that was obtained from the cloacal aperture of sea cucumber Holothuria moebii. The structures of these isolates were characterized as (11S,15R)-11-hydroxycurvularin (1), (11R,15R)-11-hydroxycurvularin (2), curvularin-7-O-α-D-glucopyranoside (3), trans-dehydrocurvularin (4) and curvularin (5) based on their NMR and HRESIMS data as well as chemical degradation. Compound 3 is a new macrolide with a rare α-D-glucopyranose substituent. Compounds 1–4, 5a and 5c (the acyl products of 5), suppressed the proliferation of all six tested cancer cell lines and 4 is the most active compound with IC₅₀ values ranging from 0.59 to 3.39 μM. The 11-hydroxycurvularins 1 and 2 also showed antibacterial activity inhibiting the growth of Escherichia coli.     

Two new xanthone glycosides from Swertia punicea Hemsl. and their anti-inflammatory activity

Abstract

Two new xanthone glycosides (1–2), together with seven known analogues (3–9), were isolated from whole herb of Swertia punicea. The structures of these metabolites were established on the basis of detailed spectroscopic analysis and comparison with data reported in the literature. In an in vitro test, all isolates were evaluated for their anti-inflammatory activity. The results revealed that all of them showed significant anti-inflammatory activity with IC₅₀ values ranging from 1.237 to 3.319?mM. Compounds 3, 4, and 5 (IC₅₀ values in the range 1.237–1.987?mM) displayed more potent anti-inflammatory activity than the positive control, indomethacin (IC₅₀ value of 2.004?mM).     

Synthesis,spectroscopic studies,antimicrobial activity,and crystal structure of a Zn(II) complex based on Voriconazole

[Zn(FZ)₂Cl₂] (1) (FZ = Voriconazole, (2R,3S)-2-(2,4-difluorophenyl)-3(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol), has been obtained through the reaction of zinc chloride and FZ and has been characterized by FT-IR, UV–vis and fluorescence spectra, elemental analysis (EA), single crystal X-ray diffraction, powder X-ray diffraction and thermogravimetric analysis (TGA). FZ was also characterized by FT-IR, UV–vis spectra, single crystal X-ray diffraction and TGA. FZ crystallizes in the chiral space group P2₁ and 1 crystallizes in chiral space group P₁ with a mononuclear structure. In 1, there are three kinds of hydrogen bonding interactions and weak stacking interactions which generate a 3-D architecture. The primary antimicrobial results show that 1 exhibits potent activity against Aspergillus (Aspergillus niger, Aspergillus terreus, Aspergillus fumigatus and Aspergillus flavus) and Candida species (Candida albicans, Candida krusei, Candida glabrata and Cryptococcus neoformans), higher than that of free FZ. Fluorescence spectra of 1 and FZ have been discussed.     

Synthesis and Antimicrobial Activities of Some 6-Methyl-3-Thioxo-2,3-Dihydro-1,2,4-Triazine Derivatives

Abstract

4-Arylidene-imidazole derivatives (4a,b) were readily prepared by reacting 4-am- ino-6-methyl-3–thioxo-2,3–dihydro[1,2,4]triazin-5(4H)-one (1) with 4-arylidene-2-phenyl- 4H-oxazol-5-one (2). Reaction of 1 with some aromatic aldehydes in presence of triethylphosphite exclusively afforded the corresponding aminophosphonates 5a-c. Reaction of 1 with 3-phenyl-1H-quinazoline-2,4-dione (6a) and/or 3-phenyl-2-thioxo-2,3-dihydro- 1H-quinazolin-4-one (6b) gave 2-(6-methyl-5-oxo-3-thioxo-2,5-dihydro-3H-[1,2,4]triazin-4-ylimino)-3-phenyl-2,3-dihydro-1H-quinazolin-4-one (7). Moreover, on treating 1 with 2-phenylbenzo[d][1,3]thiazine-4-thione (8), 6-methyl-4-(2-phenyl-4-thioxo-4H-quinazolin-3-yl)-3-thioxo-3,4-dihydro-2H-[1,2,4]triazine-5-one (9) was obtained in 65% yield. Reaction of 1 with 4-sulfonylaminoacetic acid derivatives (10a,b) afforded the corresponding sulfonamides (11a,b), respectively. Acid hydrolysis of 11a afforded 7-aminomethyl-3-methyl[1,3,4]thiadiazole[2,3-c][1,2,4]triazin-4-one (12). 4-Amino-6-methyl-3-(morpholine-4-ylsulfanyl)-4H-[1,2,4]triazin-5-one (14) was prepared by reacting compound 1 with morpholine in presence of KI/I₂, while 3,3′-bis(4-amino-6-methyl-5-oxo-triazinyl)disulfide (16) was obtained by oxidation of 1 with lead tetraacetate. The antimicrobial activity of the products was evaluated against Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]     

Palladium(II) complexes of 5-substituted isatin thiosemicarbazones: Synthesis,spectroscopic characterization,biological evaluation and in silico docking studies

Substituted heterocyclic (isatin) appended thiosemicarbazone ligands (L1–L3) are synthesized by condensation of substituted isatin molecule with N(4)-phenyl-3-thiosemicarbazide in good yields. The palladium(II) complexes are synthesized from ligands (L1–L3) and PdCl₂, with a general formula [PdCl(X-C₁₅H₁₀N₄OS)] where X?=?5-chloro (1), 5-bromo (2), and 5-nitro (3). Both analytical and spectroscopic methods have been used for the analysis and characterization of the synthesized compounds. The antimicrobial activity results observed that complexes, 1 and 2 have registered potent antibacterial activity against B. subtilis and K. pneumoniae and also complex 2 has shown good antifungal activity against the micro organisms. The antioxidant activity analysis revealed that the complex 3 showed significant activity with IC₅₀ values 7.24?±?0.09?µM. Moreover, the in vitro antiproliferative activity results suggested that complex 3 exhibited high activity against HeLa cell line compared with the standard with the IC₅₀ value 16.52?±?1.08?µM. The docking results correlate well.     

Facile synthesis of highly functionalized novel pyrazolopyridones using oxoketene dithioacetal and their anti-HIV activity

A series of novel 3-amino-4,5-dihydro-6-methyl-4-oxo-N-aryl-1H-pyrazolo[4,3-c]pyridine-7-carboxamide have been synthesized starting from various oxoketene dithioacetals. The cyclocondensation reaction of 2-(bis(methylthio)methylene)-3-oxo-N-arylbutanamide 2a–w with cyanoacetamide using NaOiPr as base under reflux condition afforded novel highly functionalized pyridone 3a–w derivatives. Further, [3?+?2] cyclocondensation reaction of pyridones with hydrazine in the presence of alcohol was yielded pyrazolopyridones (23 nos) 4a–w with excellent yields. All newly synthesized compounds were evaluated for in vitro anti-HIV activity using MTT method. Most of these compounds have showed moderate to potent activity against HIV-1 (III_B) and HIV-2 (ROD) strains with an IC₅₀ ranging from >18 IC₅₀[µg/ml] to <100 IC₅₀[µg/ml]. Among them, compounds 4j and 4v were identified as the most promising compound for both types of HIV strains. (IC₅₀?=?18?µg/ml). Three compounds 4l, 4m, and 4p have been found potent anti-HIV 1 and 2 activity against MT-4 cells.     

New dammarane and ursane-type triterpenoids from the flower of Ixora coccinea Linn.

Two new esters of dammarane triterpenoids ixorene isovalerate (1), ixorene 3′,8′-dimethyloctanoate (2) and a new ursane-type triterpenoids Ixoroid acid (3) were isolated from the methanolic extract of flowers of Ixora coccinea Linn., along with the three known constituents. The structures of compounds 1 and 3 were elucidated on the basis of extensive 1D,2D NMR studies and mass spectrometry as 17β-dammara-12,20-diene-3β-isovelarate and 3β-hydroxy-18β-urs-12ene-29β-oic acid, respectively, whereas 2 was identified as 17β-dammara-12,20-diene-3β-3′,8′-dimethyloctanoate through ¹H NMR and mass spectral data. Compounds 1, 2, 4 and 5 were evaluated for their in vitro cytotoxic activity, which exhibited weak activity against the 3T3, PC3 and HeLa cell lines with the IC₅₀ value >30 μM. Antioxidant results of 1 – 5 revealed that only compound 5 showed antioxidant activity in DPPH radical scavenging inhibition with the IC₅₀ 1.31 × 10^? 6 ± 0.005 μm mL^? 1. Both activities are the first records of these isolated compounds from the flowers of Ixora coccinea Linn.