<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Dan, Vipin Mohan</style></author><author><style face="normal" font="default" size="100%">Muralikrishnan, Balaji</style></author><author><style face="normal" font="default" size="100%">Sanawar, Rahul</style></author><author><style face="normal" font="default" size="100%">Vinodh, J. S.</style></author><author><style face="normal" font="default" size="100%">Burkul, Bhushan Bapusaheb</style></author><author><style face="normal" font="default" size="100%">Srinivas, Kalanghad Puthankalam</style></author><author><style face="normal" font="default" size="100%">Lekshmi, Asha</style></author><author><style face="normal" font="default" size="100%">Pradeep, N. S.</style></author><author><style face="normal" font="default" size="100%">Dastager, Syed G.</style></author><author><style face="normal" font="default" size="100%">Santhakumari, B.</style></author><author><style face="normal" font="default" size="100%">Santhoshkumar, Thankayyan R.</style></author><author><style face="normal" font="default" size="100%">Kumar, R. Ajay</style></author><author><style face="normal" font="default" size="100%">Pillai, Madhavan Radhakrishna</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Streptomyces sp metabolite(s) promotes Bax mediated intrinsic apoptosis and autophagy involving inhibition of mTOR pathway in cervical cancer cell lines</style></title><secondary-title><style face="normal" font="default" size="100%">Scientific Reports</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">FEB</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">8</style></volume><pages><style face="normal" font="default" size="100%">2810</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;In cervical cancer, the association between HPV infection and dysregulation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway (PI3K/AKT/mTOR pathway) places mTOR as an attractive therapeutic target. The failure of current treatment modalities in advanced stages of this cancer and drawbacks of already available mTOR inhibitors demand for novel drug candidates. In the present study we identified the presence of a mTOR inhibitor in an active fraction of the ethyl acetate extract of Streptomyces sp OA293. The metabolites(s) in the active fraction completely inhibited mTORC1 and thereby suppressed activation of both of its downstream targets, 4E-BP1 and P70S6k, in cervical cancer cells. In addition, it also stalled Akt activation via inhibition of mTORC2. The mechanism of mTOR inhibition detailed in our study overcomes significant drawbacks of well known mTOR inhibitors such as rapamycin and rapalogs. The active fraction induced autophagy and Bax mediated apoptosis suggesting that mTOR inhibition resulted in programmed cell death of cancer cells. The molecular weight determination of the components in active fraction confirmed the absence of any previously known natural mTOR inhibitor. This is the first report of complete mTOR complex inhibition by a product derived from microbial source.&lt;/p&gt;</style></abstract><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">4.259</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Siddiqui, Shaziyaparveen K.</style></author><author><style face="normal" font="default" size="100%">SahayaSheela, Vinodh J.</style></author><author><style face="normal" font="default" size="100%">Kolluru, Srinivas</style></author><author><style face="normal" font="default" size="100%">Pandian, Ganesh N.</style></author><author><style face="normal" font="default" size="100%">Santhoshkumar, Thankayyan R.</style></author><author><style face="normal" font="default" size="100%">Dan, Vipin M.</style></author><author><style face="normal" font="default" size="100%">Ramana, V, Chepuri</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Discovery of 3-(benzofuran-2-ylmethyl)-1H-indole derivatives as potential autophagy inducers in cervical cancer cells</style></title><secondary-title><style face="normal" font="default" size="100%">Bioorganic &amp; Medicinal Chemistry Letters</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Autophagy</style></keyword><keyword><style  face="normal" font="default" size="100%">Benzofuran</style></keyword><keyword><style  face="normal" font="default" size="100%">Bisindolylmethane</style></keyword><keyword><style  face="normal" font="default" size="100%">Cervical cancer</style></keyword><keyword><style  face="normal" font="default" size="100%">Friedel-Crafts alkylation</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">OCT </style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">30</style></volume><pages><style face="normal" font="default" size="100%">127431</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;In this manuscript we have documented the identification of a novel anticancer scaffold 3-(benzofuran-2-yl-methyl)-1H-indole. This scaffold has been designed by tweaking the known bisindolylmethane scaffold of natural products that display a wide range of biological activities. A series of 24 new conjugates have been synthesized and among them 5 derivatives exhibited IC50 values less than 40 mu M against two cervical cancer cell lines SiHa and C33a. Further mechanistic studies of two compounds 3eb and 3ec revealed that the toxicity of these compounds was due to the effective induction of autophagy mediated cell death. The autophagy induction was confirmed by the progressive conversion of LC3I to LC3II and downregulation of p62 in cervical cancer cells.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">19</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;Foreign&lt;/p&gt;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;2.572&lt;/p&gt;
</style></custom4></record></records></xml>