@article { ISI:000364803200011,
	title = {Design and synthesis of a focused library of diamino triazines as potential mycobacterium tuberculosis DHFR inhibitors},
	journal = {ACS Medicinal Chemistry Letters},
	volume = {6},
	number = {11},
	year = {2015},
	month = {NOV},
	pages = {1140-1144},
	publisher = {AMER CHEMICAL SOC},
	address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA},
	abstract = {<p>We report design of a series of 2,4-diamino triazines as Mycobacterium tuberculosis (Mtb) dihydrofolate reductase inhibitors. The synthesized compounds were evaluated against Mtb (H(37)Rv and Dormant stage H37Ra), their cytotoxicity was assessed (HepG2 and A549 cell lines), and selectivity toward Mtb was evaluated by testing against other bacterial strains. Some derivatives showed promising activity along with low cytotoxicity. The most potent compound in the whole cell assay (MIC 0.325 mu M against H(37)Rv) showed selectivity in the enzyme assay and exhibited synergy with second line anti-TB agent p-amino salicylic acid. This study therefore provides promising molecules for further development as antituberculosis DHFR inhibitors.</p>},
	keywords = {Diamino triazine, dihydrofolate reductase, enzyme assay, molecular modeling, Mycobacterium tuberculosis, selectivity, synergy},
	issn = {1948-5875},
	doi = {10.1021/acsmedchemlett.5b00367},
	author = {Lele, Arundhati C. and Raju, Archana and Khambete, Mihir P. and Ray, M. K. and Rajan, M. G. R. and Arkile, Manisha A. and Jadhav, Nandadeep J. and Sarkar, Dhiman and Degani, Mariam S.}
}
@article {47461,
	title = {Oxidative stress induced by piperine leads to apoptosis in Candida albicans},
	journal = {Medical Mycology},
	volume = {59},
	year = {2021},
	month = {APR},
	pages = {366-378},
	type = {Article},
	abstract = {<p>Candida albicans is a member of pathogens with potential drug resistance threat that needs novel chemotherapeutic strategies. Considering the multifarious biological activities including bioenhancer activity, anti-Candida potential of piperine was evaluated against planktonic/biofilm and hyphal growth of C. albicans alone or in combination as a synergistic agent with fluconazole. Piperine inhibits planktonic growth at or less than 15 mu g/ml, hyphae induction at 5 mu g/ml concentration, and exhibits stage-dependent activity against biofilm growth of a fluconazole-resistant strain of C. albicans (ATCC10231). Though piperine couldn{\textquoteright}t kill inoculum completely at minimum inhibitory concentration (MIC), it is fungicidal at higher concentrations, as shown in apoptosis assay. FIC index values indicate that piperine exhibits excellent synergistic activity with fluconazole against planktonic (0.123) and biofilm (0.215) growth of an FLC resistant strain. Mode of anti-Candida activity was studied by identifying piperine responsive proteins wherein the abundance of 25 proteins involved in stress response, signal transduction and cell cycle were modulated (22 up and 3 downregulated) significantly in response to piperine (MIC50). Modulation of the proteins involved suggests that piperine affectsmembrane integrity leading to oxidative stress followed by cell cycle arrest and apoptosis in C. albicans. Flow cytometry-basedmitochondrialmembrane potential (MMP), cell cycle and apoptosis assay, as well as real-time quantitative polymerase chain reaction analysis of selected genes, confirms piperine induced oxidative stress (TRR1), cell cycle arrest and apoptosis (CaMCA1). Based on our results, we conclude that piperine inhibits planktonic and difficult-to treat-biofilm growth of C. albicans by affecting membrane integrity thereby inducing oxidative stress and apoptosis. Lay Abstract Piperine inhibit Candida albicans growth (planktonic and biofilm) significantly in our study. Piperine exhibits excellent synergistic potential with fluconazole The proteome analysis suggests that piperine induced membrane damage leads to oxidative stress followed by cell cycle arrest and apoptosis.</p>},
	keywords = {Apoptosis, C. albicans, drug resistance, piperine, proteomics, synergy},
	issn = {1369-3786},
	doi = {10.1093/mmy/myaa058},
	author = {Thakre, Archana and Jadhav, Vyankatesh and Kazi, Rubina and Shelar, Amruta and Patil, Rajendra and Kharat, Kiran and Zore, Gajanan and Karuppayil, S. Mohan}
}
