Fenerbahce, has plenty of work to do in the second leg after it slipped to a damaging 2-0 defeat to Vardar in Macedonia.
Tigran Barseghyan opened the scoring before an own goal from Mehmet Topal in second-half stoppage time put Vardar in charge of the tie, with Boban Grncarov and Souza sent off for either side before full-time.
Marseille was held to a frustrating 1-1 draw away at Domzale, while there were bigger concerns for Ajax, which lost 1-0 to Rosenborg in Amsterdam thanks to a goal from substitute Samuel Adegbenro.
Meanwhile, Athletic Bilbao scored three goals in six minutes to come from two down for a 3-2 win at Panathinaikos, Aritz Aduriz scoring either side of an Oscar de Marcos strike to secure a thrilling triumph. Apollon Limassol defeated Midtjylland, which reached the last 32 two seasons ago, and Krasnodar edged out Red Star Belgrade by the same scoreline.