Novak Djokovic suffered his earliest Australian Open loss since 2006 on Thursday when the six-time champion went down in a second-round upset to Uzbek Denis Istomin 7-6 (10-8), 5-7, 2-6, 7-6 (7-5), 6-4. The Serb spent almost five hours in his struggle against a player who won an Asian qualifying competition for a spot in the draw. Istomin wrapped up the stunning upset on first match point when Djokovic hit a return long. Djokovic went down with 68 winners and 72 unforced errors to the number 117 outsider, whom he had dominated in their previous five encounters. "Denis deserved to win, no doubt, he was a better player in the clutch moments," Djokovic said. "He stepped it up, played aggressive. Served very well, very precise. There's not much I could do. "I was not pleased with my performance overall. But I have to congratulate my opponent today." It marks only his seventh loss in Melbourne against 58 wins and puts an end to any immediate chances of regaining the top ranking from Andy Murray. The pair gave notice of a marathon with a 16-minute opening game, with the first four sets going for more than four hours. Djokovic, who has not quite been himself since winning the French Open last spring to complete his career grand slam title sweep, dropped the set in a tiebreaker but won the next two. But Istomin had other plans, levelling at two apiece; the Uzbek got up a break in the fifth and never looked back. "It is the biggest win for me. It means so much," Istomin said. Djokovic said: "It's one of these days when you don't feel that great on the court, don't have much rhythm, and the player you're playing against is feeling the ball very well. "It's a tennis match. On a given day, you can lose. Nothing is impossible." There were wins for an ailing Milos Raonic, 6-3, 6-4, 7-6 (7-4) over Gilles Muller, and French sixth seed Gael Monfils who beat Alexandr Dolgopolov 6-3, 6-4, 1-6, 6-0. Belgian number 11 David Goffin accounted for veteran qualifier Radek Stepanek 6-0, 6-4, 6-3. Two more Frenchman advanced as Gilles Simon dispatched Rogerio Dutra Silva 6-4, 6-1, 6-1 and Richard Gasquet was ruthless with Carlos Berlocq 6-1, 6-1, 6-1. On the women's side, US Open finalist and fifth seed Karolina Pliskova crushed Russian Anna Blinkov 6-0, 6-2 while Slovak sixth seed Dominika Cibulkova put out Hsieh Su-Wei 6-4, 7-6 (10-8) and British ninth seed Johanna Konta beat Naomi Osaka 6-4, 6-2. Pliskova took less than an hour and did not let her opponent into the match until the fifth game. "I'm feeling pretty good on the court, confident," Pliskova said. "Even if the opponents were not that high level, I felt pretty good out there." Former world number one Caroline Wozniacki credited a new personal physiotherapist with helping her hammer Croatian Donna Vekic 6-1, 6-3, as she moved into the third round. The Dane spent several months of last season out of the sport with an ankle injury and other injuries. She has now won 27 of her last 32 matches. "I have a full-time physio with me all the time, which has really helped me," the player who topped the rankings in 2010 said. "I get treatment every day, just to keep on top of my body and help me recover, and it's really helped me a lot."