"This is a seminal moment for Angola," Piers Pigou, an analyst at the International Crisis Group, told RFI Thursday. "For the Dos Santos family to be challenged in this way is significant."
New President Joao Lourenço swore he would tackle corruption and nepotism when he was elected three months ago.
But he also agreed to reappoint his predecessor's daughter and other key allies, so the purge has taken many by surprise.
"Lourenço has had to move faster than he wanted to because of the perilous state of Angola's economy," explains Alex Vines, director of the Africa Programme at the London-based thinktank Chatham House.
Particularly the oil revenues. Oil accounts for 70 percent of the south-western African nation's economy. But the industry has been hit by crisis.
Pressure from oil companies
"Reform of Sonangol became clear that it had to occur more quickly," Vines told RFI. "Joao Lourenço has been under increasing pressure to do that from independent oil companies who were saying that, unless there were serious structural reforms, they might well move their business elsewhere."
Carlos Saturnino, the secretary of state for oil--who ironically was sacked by Isabel--has now replaced her as the head of Sonangol and the whole board has been culled.
The shake-up came as a surprise to dos Santos, who recently wrapped up a public tour where she had boasted of her track record as oil cheif and vowed to reform the state oil company.
But her nomination had already ruffled feathers.
Some Angolans saw it as an example of nepotism and a group of lawyers went to the Supreme Court last year in an attempt to get her nomination overturned.
Dos Santos sons influential
Salvador Freire, president of Angolan NGO Free Hands, was one of them.
"We believe that the power the former president gave to his family to plunder the state's resources, is coming to an end," he told RFI.
"Of course, there are still many other challenges that need to be addressed, notably the scandalous manner in which our sovereign wealth fund is being managed."
The head of Angola's sovereign wealth fund, who happens to be José Eduardo dos Santos' son, Philomene, has been beset by claims he acquired his job through nepotism and accusations of financial secrecy and was cited in the Panama Papers.
"We hope that the new leader will have the same courage to fire the former president's son as he did when he sacked his daughter," says Freire.
He has axed two of dos Santos's sons: Welwitschia "Tchizé" Dos Santos and José Paulino "Coreón Dú". Both are media moguls, whose companies had a virtual monopoly on providing content to two of Angola's state-run television stations. Their contracts were scrapped on Wednesday. The same day their sister was sacked.
MPLA faces fallout
But, with a net worth of three billion euros according to Forbes magazine, Isabel dos Santos is by far the biggest fish.
And her father is still the head of the ruling People’s Movement for the Liberation of Angola (MPLA).
"There's still the issue of when will there be an MPLA extraordinary congress which José Eduardo dos Santos will step down as head of the party," Vines points out.
But the assumption that reform could not happen until dos Santos stepped down has been proved wrong by Isabel's dismissal, according to Vines.
"Lorenço's success now will depend on him turning around the economy," he comments.