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Lung cancer is one of most common malignant cancer worldwide. It is emerging that PCYT1A, a rate-limiting enzyme required for the biosynthesis of phosphatidylcholine, is associated with cancer progression. However, the biological functions and underlying molecular mechanisms of PCYT1A in lung adenocarcinoma is still unknown. Here we found that PCYT1A suppressed lung adenocarcinoma cancer cell proliferation and migration. Mechanically, PCYT1A served as a novel negative regulator of mTORC1 signaling. PCYT1A knockdown enhanced the malignant proliferation and migration of lung adenocarcinoma cells by activating mTORC1. The promoting effects of PCYT1A silencing on cell proliferation and migration could be abolished when mTORC1 signaling was inhibited by rapamycin or RAPTOR depletion. Importantly, PCYT1A high expression predicted longer survival of lung cancer patients. The expression of PCYT1A was also negatively correlated with mTORC1 activation in the clinical lung cancer samples. We therefore reveal that PCYT1A suppresses proliferation and migration by inhibiting the mTORC1 signaling pathway in lung adenocarcinoma. PCYT1A shows as a potential promising biomarker in lung adenocarcinoma. PCYT1A inhibits mTORC1 activation to suppress lung adenocarcinoma cell proliferation and migration. Low expression of PCYT1A by knocking down PCYT1A activates mTORC1 signaling thereby promoting cell proliferation and migration in lung adenocarcinoma cells, which can be reversed by mTORC1 inhibition by Rapamycin or RAPTOR knockdown. mTORC1 activation is negatively correlated with PCYT1A expression in lung adenocarcinoma clinical samples, revealing that PCYT1A/mTORC1 axis may be a potential target for lung cancer treatment. Image 1 • PCYT1A suppresses proliferation and migration in lung adenocarcinoma. • PCYT1A suppresses the malignant biological behavior in a mTORC1 dependent manner in lung adenocarcinoma. • PCYT1A is negatively correlated with mTORC1 activation in lung cancer clinical samples. • PCYT1A/mTORC1 axis may be a potential target for lung cancer treatment. [ABSTRACT FROM AUTHOR]

• Twenty-eight chromanone-dithiocarbamate hybrids were designed and synthesized. • 6c showed potential inhibition for both AChE and Aβ aggregation. • 6c exhibited no acute toxicity in mice and could penetrate the BBB. • 6c could significantly reverse scopolamine-induced memory deficit in vivo. By connecting chromanone with dithiocarbamate moieties through flexible linkers, a series of hybrids as novel multifunctional AChE inhibitors have been designed and synthesized. Most of these compounds displayed strong and excellently selective inhibition to eeAChE as well as potent inhibition to self- and AChE-induced Aβ aggregation. Among them, compound 6c showed the best activity to inhibit eeAChE (IC 50 = 0.10 μM) and AChE-induced Aβ aggregation (33.02% at 100 μM), and could effectively inhibit self-induced Aβ aggregation (38.25% at 25 μM). Kinetic analysis and docking study indicated that compound 6c could target both the CAS and PAS, suggesting that it was a dual binding site inhibitor for AChE. Besides, it exhibited good ability to penetrate the BBB and low neurotoxicity in SH-SY5Y cells. More importantly, compound 6c was well tolerated in mice (2500 mg/kg, po) and could attenuate the memory impairment in a scopolamine-induced mouse model. Overall, these results highlight 6c as a promising multifunctional agent for treating AD and also demonstrate that the dithiocarbamate is a valid scaffold for design of multifunctional AChE inhibitors. [ABSTRACT FROM AUTHOR]