Syria's uprising has entered a dramatic new phase as rebels fighting the regime of Bashar al-Assad killed three of his top security chiefs in a devastating bomb attack in the heart of Damascus.

Syrian state TV confirmed the death of Assef Shawkat, Assad's brother-in-law and the deputy head of the armed forces, and his closest security adviser, as well as Dawoud Rajha, the minister of defence and the regime's most senior Christian figure. Hassan Turkmani, its crisis management chief, was also killed.

Several other key figures, including the interior minister, Mohammed Shaar, were wounded and being treated in the capital's al-Shami hospital.

Explosions were also reported from the headquarters of the army's 4th division in Damascus – the regime's elite unit commanded by Assad's brother Maher.

Sergei Lavrov, Russia's foreign minister, said a "decisive battle" had begun in Syria. Lavrov also made clear Moscow would oppose a draft UN security council resolution threatening punishment if Assad did not implement the UN-backed peace plan promoted by Kofi Annan.

The attack on the headquarters of Syria's national security council in the al-Rawda area was the most audacious yet by anti-Assad rebels, who have been fighting sporadically in parts of the capital for the past four days.

It was not clear whether it was a suicide bombing but it was rumoured that the suspected killer may have been a bodyguard for Rajha or another member of Assad's inner circle. But one pro-regime source in Damascus told the Guardian it was possible that a bomb could have planted on the premises.

The attack was a deadly blow to the heart of the regime after two recent high-level defections – by a senior Republican Guard commander and Syria's ambassador to Iraq.

Syrian state TV said foreign-backed "terrorists" had carried out the attack. The country's armed forces said in a statement that Syria was "more determined than ever to confront all forms of terrorism and chop off any hand that harms national security".

Syrian state TV also reported that the military would on Thursday morning call up its reserve forces. Replacements for the three dead men were quickly announced.

Rumours spread wildly in the hours after the incident and information was impossible to verify. According to one pro-government source rebels of the Free Syrian Army (FSA) started moving around in pick-up trucks to show they controlled parts of the city. Ba'ath party members had been executed by FSA men, the source said.

There were also widespread reports of defections in many areas of Syria including central Damascus as well as Homs and Hama. Activists reported that several tanks had been abandoned near the centre of the capital and that several combat units had defected en masse. These reports could not be independently confirmed.

Shawkat, married to Assad's sister Bushra, was one of the most feared figures in the president's inner circle and had won the support of the clan's influential matriarch, Anisa. He was one of three central figures in the regime crackdown, along with Assad himself and his brother Maher. As Syria's overall security chief, he had key input into all military and intelligence operations. He is known to have survived an attempt to poison him in late May when a cook contaminated food that had been prepared for him and key members of the national security ministry.

Abu Hamza of the Free Syrian Army told the Guardian at the time that rebel forces were trying to recruit aides of regime figures to carry out future attacks. "We have had some success with this," he said. "Some have been with us for a long time and have not yet been given orders to move."

Shawkat had also been a key point-man with Iran and with Hezbollah. Since the uprising started he had chaired key strategy meetings and had driven the regime's uncompromising and aggressive military response to the escalating dissent.

Rajha, a former general, was appointed defence minister last year in an apparent attempt to emphasise the inclusiveness of the Alawite-dominated regime.

Prospects for any kind of negotiation between the government and rebels – always slim – have now disappeared.

Pro-regime Syrians appeared shocked by the news. "A lot of pro-Assad people are really panicking," said an opposition activist. "Now they sound really nervous."

Assad supporters admitted the attack was a serious blow. "This will not be the end of the regime in any way," said one member of Assad's Alawite community. "But it is serious and people are traumatised at the fact that the opposition managed to assassinate these people. But government supporters want the government to be firm and show it is still in control. The Syrian government is not usually impulsive."