BEIRUT, Lebanon (AP) — A bomb ripped through a high-level security meeting yesterday in Damascus, killing three top regime officials — including President Bashar Assad's brother-in-law — in the harshest blow to Syria's ruling family dynasty and the rebels' boldest attack in the country's civil war.

Syrian state-run TV said the blast came during a meeting of Cabinet ministers and senior security officials in the capital, where fighting between rebels and government troops has raged for four straight days.

The assassinations could signal a turning point in the civil war following some of the worst bloodshed that Damascus has seen in the 16-month uprising, the growing list of high-ranking defections from the regime and the increasing frustration by world leaders over their inability to find a diplomatic solution.

US Defense Secretary Leon Panetta said the bombing showed that the bloodshed in Syria was "rapidly spinning out of control," and it was time for the international community to bring "maximum pressure" on Assad to step down and permit a stable transfer of power. The Obama administration also slapped new financial sanctions on Assad's government.

It was not immediately clear where Assad was. He gave no immediate statements on the attacks.

The Assad family has ruled Syria for four decades, creating an ironclad and impenetrable regime. Yesterday's attack was an unheard-of strike on the inner circle.

Syria's rebel commander, Riad al-Asaad, claimed responsibility, saying his rebel forces planted a bomb in the room and detonated it. All those involved in carrying out the attack are safe, he said.

State-run TV initially said it was a suicide blast but later referred to the attack as a bomb.

"God willing, this is the beginning of the end of the regime," al-Asaad told The Associated Press in a telephone interview from his base in neighbouring Turkey.

"Hopefully Bashar will be next," he added.

Syrian TV confirmed the deaths of Defense Minister Dawoud Rajha, 65, a former army general and the most senior government official to be killed in the rebels' battle to oust Assad; General Assef Shawkat, the deputy defence minister who is married to Assad's elder sister, Bushra, and is one of the most feared figures in the inner circle; and Hassan Turkmani, a former defence minister who died of wounds suffered in the attack.

Also wounded were Interior Minister Mohammed Shaar and Major General Hisham Ikhtiar, who heads the National Security Department. State TV said both were in stable condition.

Although there were no statements from Assad, Syrian TV said in the hours after the attack that a decree from him named General Fahd Jassem al-Freij as the new defence minister. Al-Freij used to be the army chief of staff.

A member of the Syrian National Council opposition group, Omar Shawaf, said the assassinations sent a clear message to the regime that no one is safe — including Assad himself.

"The hands of the Syrian people and the Free Syrian Army can reach anyone inside Damascus," he said from Turkey, where he is based.