Zamalek's hopes to qualify for the African Champions League quarters were dealt a blow after they extended their winless start to Group D with a 3-1 loss at Tunisia's Esperance in Rades on Saturday.
Ivorian striker William Togui put Esperance ahead against the run of play but Zamalek's left-back Ahmed Aboul-Fotouh, who was at fault for the hosts' opening goal, equalised with a powerful finish five minutes before the break.
Ali Ben Romdhane restored Esperance's advantage from the spot on the stroke of halftime before wrapping up the win seven minutes into the second period after finishing off a breakaway.
Zamalek's hopes to get something out of the game were further dampened after Aboul-Fotouh was sent off on 57 minutes for a second bookable offence, with Esperance assuming full control afterwards.
The defeat will increase pressure on Zamalek's beleaguered coach Jaime Pacheco, whose side suffered a notable dip in form following the departure of marksman Mostafa Mohamed, who joined Turkish side Galatasaray on loan in January. Since then, Zamalek's misfiring strikers have failed to find the net.
Zamalek, who were held to two opening 0-0 draws before losing to Esperance, are third in the group with two points, three behind MC Alger, who defeated bottom side Teungueth FC 1-0 in Senegal. Esperance top the group with seven points.
With MC Alger facing a straightforward task at home to Teungueth in the next round, Zamalek could face an uphill climb to reach the knockout stage. They next host Esperance in Cairo later this month.
Although the visitors had the better of the early exchanges, it was Esperance who went ahead on 26 minutes when ex-Zamalek full-back Hamdi Nagguez bamboozled Aboul-Fotouh down the flank and ran to the byline.
He pulled the ball back to the unmarked Togui to side-foot the ball into the bottom corner.
Off-form forward Hamid Ahadad wasted Zamalek's first real chance on 32 minutes when he could only fire straight at the keeper from close range after a cut-back from winger Ahmed Zizo.
Aboul-Fotouh drew Zamalek level in the 40th minute when Ferjani Sassi left his challenger on the floor with a nice piece of individual skill near the byline before pulling the ball back to the Egyptian international, who blasted a powerful effort into the far corner despite using his weak right foot.
Zamalek's joy was short-lived, however, with Ben Romdhane sending keeper Mahmoud Gennesh the wrong way after defender Mohamed Abdel-Ghani clumsily brought down Abdelraouf Benguit.
Ben Romdhane netted again in the 53rd minute in a carbon copy of the opener and substitute Anice Badri spurned two chances to extend their lead as Esperance exacted revenge on Zamalek, who defeated them in the African Super Cup and knocked them out of the Champions League quarters last season.
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