@article { ISI:000308046400038, title = {Hybrid molecules of carvacrol and benzoyl urea/thiourea with potential applications in agriculture and medicine}, journal = {Bioorganic \& Medicinal Chemistry Letters}, volume = {22}, number = {17}, year = {2012}, month = {SEP}, pages = {5550-5554}, publisher = {PERGAMON-ELSEVIER SCIENCE LTD}, address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND}, abstract = {

Benzoyl phenyl urea, a class of insect growth regulator{\textquoteright}s acts by inhibiting chitin synthesis. Carvacrol, a naturally occurring monoterpenoid is an effective antifungal agent. We have structurally modified carvacrol (2-methyl-5-[1-methylethyl] phenol) by introducing benzoylphenyl urea linkage. Two series of benzoylcarvacryl thiourea (BCTU, 4a-f) and benzoylcarvacryl urea (BCU, 5a-f) derivatives were prepared and characterized by elemental analysis, IR, H-1 and C-13 NMR and Mass spectroscopy. Derivatives 4b, 4d, 4e, 4f and 5d, 5f showed comparable insecticidal activity with the standard BPU lufenuron against Dysdercus koenigii. BCTU derivatives 4c, 4e and BCU 5c showed good antifungal activity against phytopathogenic fungi viz. Magnaporthe grisae, Fusarium oxysporum, Dreschlera oryzae; food spoilage yeasts viz. Debaromyces hansenii, Pichia membranifaciens; and human pathogens viz. Candida albicans and Cryptococcus neoformans. Compounds 5d, 5e and 5f showed potent activity against human pathogens. Moderate and selective activity was observed for other compounds. All the synthesized compounds were non-haemolytic. These compounds have potential application in agriculture and medicine. (C) 2012 Elsevier Ltd. All rights reserved.

}, keywords = {Antifungal agents, Benzoyl carvacryl urea, Benzoyl phenyl urea, Crop protection agents, Insect growth regulators}, issn = {0960-894X}, doi = {10.1016/j.bmcl.2012.07.017}, author = {Pete, Umesh D. and Zade, Chetan M. and Bhosale, Jitendra D. and Tupe, Santosh G. and Chaudhary, Preeti M. and Dikundwar, Amol G. and Bendre, Ratnamala S.} } @article { ISI:000317204600005, title = {Chitin synthase inhibitors as antifungal agents}, journal = {Mini-Reviews in Medicinal Chemistry}, volume = {13}, number = {2}, year = {2013}, month = {FEB}, pages = {222-236}, publisher = {BENTHAM SCIENCE PUBL LTD}, address = {EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES}, abstract = {

Increased risk of fungal diseases in immunocompromised patients, emerging fungal pathogens, limited repertoire of antifungal drugs and resistance development against the drugs demands for development of new and effective antifungal agents. With greater knowledge of fungal metabolism efforts are being made to inhibit specific enzymes involved in different biochemical pathways for the development of antifungal drugs. Chitin synthase is one such promising target as it is absent in plants and mammals. Nikkomycin Z, a chitin synthase inhibitor is under clinical development. Chitin synthesis in fungi, chitin synthase as a target for antifungal agent development, different chitin synthase inhibitors isolated from natural sources, randomly synthesized and modified from nikkomycin and polyoxin are discussed in this review.

}, keywords = {Antifungal agents, Chitin synthase, Chitin synthase inhibitors, Nikkomycin, Peptidyl nucleoside antibiotics, Polyoxin}, issn = {1389-5575}, author = {Chaudhary, Preeti M. and Tupe, Santosh G. and Deshpande, Mukund V.} } @article { ISI:000340300300018, title = {Antifungal activity and mechanism of action of carvacrol and thymol against vineyard and wine spoilage yeasts}, journal = {Food Control}, volume = {46}, year = {2014}, month = {DEC}, pages = {115-120}, publisher = {ELSEVIER SCI LTD}, type = {Article}, address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND}, abstract = {

Antimicrobial activity of carvacrol and thymol against natural yeast flora of the grapes and yeasts known to cause wine spoilage was examined. Carvacrol and thymol exhibited comparable or better antifungal activity than potassium metabisulphite, commercially used wine preservative, against the natural yeast flora and spoilage yeasts. The antifungal activity for both the compounds was better at pH 3.5 than pH 6.5. Addition of carvacrol and thymol (64 mu g/mL) in red wine resulted in inhibition of growth of the spoilage yeasts. Carvacrol and thymol exerted their antimicrobial action through membrane damage, leakage of cytoplasmic content and ergosterol depletion. In conclusion, carvacrol and thymol holds promise as a potential natural preservative for the control of wine spoilage. (C) 2014 Elsevier Ltd. All rights reserved.

}, keywords = {antifungal, Carvacrol, Thymol, Wine spoilage}, issn = {0956-7135}, doi = {10.1016/j.foodcont.2014.05.007}, author = {Chavan, Pradnya S. and Tupe, Santosh G.} } @article { ISI:000333939500005, title = {Antifungal dimeric chalcone derivative kamalachalcone E from Mallotus philippinensis}, journal = {Natural Product Research}, volume = {28}, number = {4}, year = {2014}, month = {FEB}, pages = {245-250}, publisher = {TAYLOR \& FRANCIS LTD}, type = {Article}, address = {4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND}, abstract = {

From the red coloured extract (Kamala) prepared through acetone extraction of the fresh whole uncrushed fruits of Mallotus philippinensis, one new dimeric chalcone (1) along with three known compounds 1-(5,7-dihydroxy-2,2,6-trimethyl-2H-1-benzopyran-8-yl)-3-phenyl-2-propen -1-one (2), rottlerin (3) and 4 {\textquoteleft}-hydroxyrottlerin (4) were isolated. The structure of compound 1 was elucidated by 1D and 2D NMR analyses that included HSQC, HMBC, COSY and ROESY experiments along with the literature comparison. Compounds 1-4 were evaluated for antifungal activity against different human pathogenic yeasts and filamentous fungi. The antiproliferative activity of the compounds was evaluated against Thp-1 cell lines. Compounds 1 and 2 both exhibited IC50 of 8, 4 and 16 mu g/mL against Cryptococcus neoformans PRL518, C. neoformans ATCC32045 and Aspergillus fumigatus, respectively. Compound 4, at 100 mu g/mL, showed 54\% growth inhibition of Thp-1 cell lines.

}, keywords = {4 {\textquoteleft}-hydroxyrottlerin, antifungal, dimeric chalcone, kamalachalcone E, Mallotus philippinensis, rottlerin}, issn = {1478-6419}, doi = {10.1080/14786419.2013.843178}, author = {Kulkarni, Roshan R. and Tupe, Santosh G. and Gample, Suvarna P. and Chandgude, Macchindra G. and Sarkar, Dhiman and Deshpande, Mukund V. and Joshi, Swati P.} } @article { ISI:000364803200006, title = {Silicon incorporated morpholine antifungals: design, synthesis, and biological evaluation}, journal = {ACS Medicinal Chemistry Letters}, volume = {6}, number = {11}, year = {2015}, month = {NOV}, pages = {1111-1116}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

Known morpholine class antifungals (fenpropimorph, fenpropidin, and amorolfine) were synthetically modified through silicon incorporation to have 15 sila-analogues. Twelve sila-analogues exhibited potent antifungal activity against different human fungal pathogens such as Candida albicans, Candida glabrata, Candida tropicalis, Cryptococcus neoformans, and Aspergillus niger. Si la-analogue 24 (fenpropimorph analogue) was the best in our hands, which showed superior fungicidal potential than fenpropidin, fenpropimorph, and amorolfine. The mode of action of sila-analogues was similar to morpholines, i.e., inhibition of sterol reductase and sterol isomerase enzymes of ergosterol synthesis pathway.

}, keywords = {Antifungal drugs, Candida albicans, ergosterol biosynthesis, morpholines, sila-analogues}, issn = {1948-5875}, doi = {10.1021/acsmedchemlett.5b00245}, author = {Jachak, Gorakhnath R. and Ramesh, Remya and Sant, Duhita G. and Jorwekar, Shweta U. and Jadhav, Manjusha R. and Tupe, Santosh G. and Deshpande, Mukund V. and Reddy, D. Srinivasa} } @article { ISI:000358338300003, title = {Synthesis and antifungal potential of 1,2,3-triazole and 1,2,4-triazole thiol substituted strobilurin derivatives}, journal = {Indian Journal of Chemistry Section B-Organic Chemistry Including Medicinal Chemistry}, volume = {54}, number = {7}, year = {2015}, month = {JUL}, pages = {908-917}, publisher = {COUNCIL SCIENTIFIC \& INDUSTRIAL RES}, address = {ANUSANDHAN BHAWAN, 2 RAFI MARG, NEW DELHI, 110001, INDIA}, abstract = {

beta-Methoxyacrylate group is an important pharmacophore of commercially used strobilurin fungicides. In the present study, a total of seventeen 1,2,4-triazole thiols 8a-h and 1,2,3-triazole substituted 10a-i strobilurin derivatives have been synthesized. 1,2,4-Triazole thiol substituted strobilurin derivatives 8a-h have been found to inhibit the growth of plant pathogens such as Fusarium oxysporum, Magnaporthe grisea, Drechslera oryzae and human pathogens Aspergillus fumigatus and different strains of Cryptococcus neoformans, with MIC in the range of 16-256 mu g/mL. In case of Candida albicans tested strain, the MIC is \> 256 mu g/mL. p-Chlorophenyl substituted 1,2,4-triazole thiol strobiulrin derivative 8e is the most potent inhibitor with MIC of 16-64 mu g/mL against most of the tested pathogens. Antifungal action of the compounds is due to inhibition of mitochondrial respiration. In the resazurin reduction assay, EC50 for inhibition of RZ reduction in D. oryzae by azoxystrobin and 8e are 3.42 +/- 0.03 mu g/mL and 3.63 +/- 0.21 mu g/mL, respectively; while in case of C. neoformans, EC50,, of azoxystrobin and 8e are between 0.65-0.85 mu g/mL. In a non-pathogenic model Benjaminiella poitrasii, though the MIC for all the synthesized compounds 8a-h and 10a-i are \> 256 mu g/ml, yeast to hypha transition is inhibited in the range of 21-75\% at 4 mu g/mL concentration while EC50 for inhibition of RZ reduction by azoxystrobin and 8e are 31.5 +/- 0.4 mu g/mL and 17.95 +/- 0.7 mu g/mL, respectively. The 50\% germ tube formation inhibition in case of C. albicans is observed at 108.49 mu g/mL. 1,2,4-Triazole thiol substituted strobilurin derivatives hold promise for the control of pathogenic fungi in agriculture and health care.

}, keywords = {1, 2, 3-triazole strobilurin, 4-triazole thiol strobilurin, antifungal, Strobilurin, Y-H transition inhibition}, issn = {0376-4699}, author = {Chaudhary, Preeti M. and Tupe, Santosh G. and Jorwekar, Shweta U. and Sant, Duhita G. and Deshpande, Sunita R. and Maybhate, Shailaja P. and Likhite, Anjali P. and Deshpande, Mukund V.} } @article { ISI:000369545400074, title = {Re-engineering of PIP3-antagonist triazole PITENIN{\textquoteright}s chemical scaffold: development of novel antifungal leads}, journal = {RSC Advances}, volume = {6}, number = {14}, year = {2016}, month = {JAN}, pages = {11691-11701}, publisher = {ROYAL SOC CHEMISTRY}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

A novel 4-(1-phenyl-1-hydroxyethyl)-1-(o-hydroxyphenyl)-1H-1,2,3-triazole was designed by integrating the structural features of triazole PITENIN anticancer agents and the azole class of antifungal drugs. A two-step protocol comprising the Barbier propargylation and Cu-catalyzed azide-alkyne cycloaddition was established to synthesise a diverse set of compounds of this class. Their screening against a wide range of human fungal pathogens led to identification of several potential antifungal hits and some of them displayed better antifungal activity than fluconazole against Candida glabrata, Cryptococcus neoformans, Aspergillus fumigatus and Aspergillus niger. Mode of action studies revealed that their antifungal activity was resulting either from the inhibition of lanosterol 14 alpha-demethylase enzyme (leading to ergosterol depletion) or by the generation of reactive oxygen species (ROS).

}, issn = {2046-2069}, doi = {10.1039/c5ra25145a}, author = {Pulya, Sravani and Kommagalla, Yadagiri and Sant, Duhita G. and Jorwekar, Shweta U. and Tupe, Santosh G. and Deshpande, Mukund V. and Ramana, Chepuri V.} } @article { ISI:000380241600003, title = {Ultrasound- and molecular sieves-assisted synthesis, molecular docking and antifungal evaluation of 5-(4-(benzyloxy)-substituted phenyl)-3-((phenylamino)methyl)-1,3,4-oxadiazole-2(3H)-thiones}, journal = {Molecules}, volume = {21}, number = {5}, year = {2016}, month = {MAY}, pages = {484}, publisher = {MDPI AG}, address = {ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND}, abstract = {

A novel series of 5-(4-(benzyloxy) substituted phenyl)-3-((phenyl amino) methyl)-1,3,4-oxadiazole-2(3H)-thione Mannich bases 6a-o were synthesized in good yield from the key compound 5-(4-(benzyloxy) phenyl)-1,3,4-oxadiazole-2(3H)-thione by aminomethylation with paraformaldehyde and substituted amines using molecular sieves and sonication as green chemistry tools. The antifungal activity of the new products was evaluated against seven human pathogenic fungal strains, namely, Candida albicans ATCC 24433, Candida albicans ATCC 10231, Candida glabrata NCYC 388, Cryptococcus neoformans ATCC 34664, Cryptococcus neoformans PRL 518, Aspergillus fumigatus NCIM 902 and Aspergillus niger ATCC 10578. The synthesized compounds 6d, 6f, 6g, 6h and 6j exhibited promising antifungal activity against the tested fungal pathogens. In molecular docking studies, derivatives 6c, 6f and 6i showed good binding at the active site of C. albicans cytochrome P450 enzyme lanosterol 14 alpha-demethylase. The in vitro antifungal activity results and docking studies indicated that the synthesized compounds have potential antifungal activity and can be further optimized as privileged scaffolds to design and develop potent antifungal drugs.

}, keywords = {1, 3, 4-oxadiazoles, Antifungal activity, Mannich reaction, Molecular docking, Molecular sieves, Ultrasound}, issn = {1420-3049}, doi = {10.3390/molecules21050484}, author = {Nimbalkar, Urja D. and Tupe, Santosh G. and Seijas Vazquez, Julio A. and Khan, Firoz A. Kalam and Sangshetti, Jaiprakash N. and Nikalje, Anna Pratima G.} } @article {43853, title = {Development of metarhizium anisopliae as a mycoinsecticide: from isolation to field performance}, journal = {Jove-Journal of Visualized Experiments}, year = {2017}, month = {JUL}, pages = {Article Number: e55272}, type = {Article}, abstract = {A major concern when developing commercial mycoinsecticides is the kill speed compared to that of chemical insecticides. Therefore, isolation and screening for the selection of a fast-acting, highly virulent entomopathogenic fungus are important steps. Entomopathogenic fungi, such as Metarhizium, Beauveria, and Nomurea, which act by contact, are better suited than Bacillus thuringiensis or nucleopolyhedrosis virus (NPV), which must be ingested by the insect pest. In the present work, we isolated 68 Metarhizium strains from infected insects using a soil dilution and bait method. The isolates were identified by the amplification and sequencing of the ITS1-5.8S-ITS2 and 26S rDNA region. The most virulent strain of Metarhizium anisopliae was selected based on the median lethal concentration (LC50) and time (LT50) obtained in insect bioassays against III-instar larvae of Helicoverpa armigera. The mass production of spores by the selected strain was carried out with solid-state fermentation (SSF) using rice as a substrate for 14 days. Spores were extracted from the sporulated biomass using 0.1\% tween-80, and different formulations of the spores were prepared. Field trials of the formulations for the control of an H. armigera infestation in pigeon peas were carried out by randomized block design. The infestation control levels obtained with oil and aqueous formulations (78.0\% and 70.9\%, respectively) were better than the 63.4\% obtained with chemical pesticide.}, doi = {10.3791/55272}, author = {Tupe, Santosh G. and Pathan, Ejaj K. and Deshpande, Mukund V.} } @article {42938, title = {Synthesis and biological evaluation of new fluconazole β-lactam conjugates linked via 1,2,3-triazole}, journal = {New Journal of Chemistry}, volume = {41}, year = {2017}, month = {FEB}, pages = {470-479}, abstract = {

Novel 1,2,3-triazole-linked β-lactam{\textendash}fluconazole conjugates 12(a{\textendash}l) were designed and synthesized. The compounds showed potent antifungal activity against two pathogenic Candida strains; Candida albicans ATCC 24433 and Candida albicans ATCC 10231 with MIC values in the range of 0.0625{\textendash}2 μg mL-1. Compounds 12h, 12j and 12k showed promising antifungal activity against all the tested fungal pathogens except C. neoformans ATCC 34554 compared to fluconazole. Compound 12j in which the β-lactam ring was formed using para-anisidine and benzaldehyde was found to be more potent than fluconazole against all the fungal strains with an IC50 value of \<0.015 μg mL-1 for Candida albicans (ATCC 24433). Mechanistic studies for active compounds revealed that the antifungal action was due to ergosterol inhibition. Compounds 12h and 12j at a concentration of 0.125 μg mL-1 caused 91.5 and 96.8\% ergosterol depletion, respectively, compared to fluconazole which at the same concentration caused 49\% ergosterol depletion. The molecular docking study revealed that all the fluconazole β-lactam conjugates 12(a{\textendash}l) could snugly fit into the active site of lanosterol 14α-demethylase (CYP51) with varying degrees of affinities. As anticipated, the binding energy for compound 12j (-58.961 kcal mol-1) was much smaller than that for fluconazole (-52.92 kcal mol-1). The synthesized compounds have therapeutic potential for the control of candidemia.

}, doi = {10.1039/C6NJ03117J}, author = {Divse, Jaisingh M. and Mhaske, Santosh B. and Charolkar, Chaitanya R. and Sant, Duhita G. and Tupe, Santosh G. and Deshpande, Mukund V. and Khedkar, Vijay M. and Nawale, Laxman U. and Sarkar, Dhiman and Pore, Vandana S.} } @article {44476, title = {Facile and solvent-free domino synthesis of new quinolidinyl-2,4-thiazolidinones: antifungal activityand molecular docking}, journal = {Mini-Reviews in Medicinal Chemistry}, volume = {18}, year = {2018}, month = {JAN}, pages = {622-630}, abstract = {Objective: We have synthesized new quinolidinyl-thiazolidinones via Knoevenagel condensation-alkylation reaction, catalyzed by [Et3NH][HSO4]. The present approach offers several advantages such as higher yields, eco-friendly reaction condition and economic availability of the catalyst. Method: The newly synthesized compounds were evaluated for their in vitro antifungal activity against six fungal strains. Some of the synthesized conjugates displayed good to moderate antifungal activity. Conclusion: Again, the molecular docking study performed against the fungal sterol 14 alpha-demethylase (CYP51) showed an excellent binding affinity towards the enzyme which could rationalize the promising antifungal activity portrayed by these derivatives and provides a platform for structure based drug design.}, doi = {10.2174/1389557516666161226161152}, author = {Subhedar, Dnyaneshwar D. and Shaikh, Mubarak H. and Tupe, Santosh G. and Deshpande, Mukund V. and Khedkar, Vijay M. and Jha, Prakash C. and Shingate, Bapurao B.} }