Nearly 100 people were killed on Wednesday in violence across Syria, including 16 in Damascus, said the Syrian Observatory for Human Rights.
The Britain-based watchdog reported that 97 people were killed across Syria, including 46 civilians, eight rebel fighters and 43 regime troops. All but one of those killed in the capital were civilians.
Violence engulfed Damascus for a fourth straight day as a bombing killed three of the regime's top security chiefs who were meeting at the National Security headquarters, in an attack claimed by the rebel Free Syrian Army.
A suicide bomber on Wednesday struck at the heart of Syria's security apparatus, killing the country's defence minister and Al-Assad's brother-in-law, state television said.
The interior minister has also been reported dead, following initial reports of his injury.
The attack, which for the first time in a 16-month armed anti-regime insurgency targeted members of Al-Assad's inner core, came hours ahead of a previously scheduled UN Security Council debate on Syrian sanctions, where a showdown between Western powers and Russia and China had been expected.
Officials said the bomber struck as ministers and security officials were meeting at the heavily guarded National Security headquarters in Damascus.
Defence minister General Daoud Rajha, Al-Assad's brother-in-law Assef Shawkat and Interior Minister Mohammed al-Shaar were all reported killed, the channel and security officials said.
General Hassan Turkmani, a former defence minister and senior military official, also died of wounds sustained in the bomb attack.
Head of national security, General Hisham Ikhtiyar, was wounded.
Syria's rebel Free Syrian Army (FSA) claimed responsibility for the deadly attack.
The FSA command "announces the good news of the outstanding operation this morning that targeted the National Security headquarters and the killing" of the officials "responsible for barbaric massacres," it said in a statement.
"FSA fighters welcomed the news of the killing of the three officials by telling regime troops to defect from the army before the regime falls," an activist in Al-Midan who identified himself as Ahmed told AFP via Skype.
The Syrian Observatory for Human Rights called Shawkat's death "a severe blow to the Syrian regime since he played the main role in operations by regular forces to crush the revolution."
Later Wednesday, Syrian state television reported that Al-Assad had appointed Fahd Al-Freij as new defence minister, while Syria's army vowed to "continue fighting terrorism."
"The terrorist act increases the armed forces' determination to clean the country of terrorist groups," it said in a statement.
Rajha, a Christian, was defence minister, deputy army chief and deputy head of the Council of Ministers. Al-Assad himself is overall commander of the military.
Shawkat was deputy defence minister and a former military intelligence chief.
The National Security branch headed by General Ikhtiyar is a linchpin of Syria's security apparatus.
Battles rage across Syria
The brazen attack on regime insiders came as battles raged throughout Wednesday day across Damascus and after the FSA – comprising defected soldiers and civilians who have taken up arms against Al-Assad's forces – warned the government to "expect surprises."
Columns of black smoke rose over the capital, with the Local Coordination Committees, which organises anti-regime protests on the ground, reporting that the Qaboon and Barzeh neighbourhoods had been bombarded by loyalist forces.
It also said there was less traffic than normal in the city where fighting has raged since Sunday, with the rebels announcing a full-scale offensive dubbed "the Damascus volcano and earthquakes of Syria."
Regime forces and the FSA clashed in the Al-Midan and Zahira districts of Damascus as well as at Assali south of the city, the LCC said.
By Wednesday evening, the Observatory reported clashes across the southern, eastern and western outskirts of Damascus, with the most intense fighting in Al-Midan near the city centre.
Clashes also broke out during the day on the edges of Palestinian refugee camp Yarmuk, the Observatory's Rami Abdel Rahman told AFP.
Residents of the camp said they feared a major onslaught as violence came closer to their neighbourhood, which has become a place of refuge for people fleeing nearby violence-stricken districts.
Troops also shelled besieged districts of the central city of Homs on Wednesday, the Observatory said, adding violence also struck the nearby city of Hama, where five civilians were killed.
"In some areas of Hama there are snipers everywhere and they are shooting at anything that moves," a Hama-based activist told AFP via Skype. "In other areas, people are handing out sweets to celebrate" the death of the three regime officials.
Rebel forces on Tuesday had said the battle to "liberate" Damascus had begun, as heavy fighting raged with the regime using helicopter gunships in the capital for the first time.
FSA spokesman Colonel Kassem Saadeddine had said that "victory is nigh" and that the struggle would go on until the city was conquered.
"We have transferred the battle from Damascus province to the capital. We have a clear plan to control the whole of Damascus. We only have light weapons, but it's enough."
"Expect surprises," Saadeddine added.
Arab League reactions
Arab League chief Nabil El-Arabi has described Wednesday's bomb attack in the Syrian capital Damascus as a "major development."
El-Arabi also voiced the pan-Arab organisation's concern over the deteriorating humanitarian situation in Syria, warning of the mounting threat of civil war. "Violence leads to more violence," he said.
The Arab League chief went on to call for the peaceful, democratic transition of power in Syria, saying that respect for the Syrian people's legitimate rights was "the only safe exit" from the ongoing bloodshed.
According to El-Arabi, Arab foreign ministers will hold an emergency meeting on Sunday to discuss the crisis in Syria.
The planned meeting in Doha, Qatar, which will follow a scheduled session of the organisation's Syria crisis taskforce, will "examine the consequences of the situation in Syria from all angles," El-Arabi said.
US Defence Secretary Leon Panetta warned on Wednesday that the situation in Syria was "spinning out of control."
The international community must "bring maximum pressure on Al-Assad to do what's right, to step down and to allow for that peaceful transition," Panetta told reporters.
In Bejing, UN chief Ban Ki-moon urged the Security Council to act to stop the bloodshed in Syria, after holding talks ahead of a vote on fresh sanctions.
Ban said the Security Council must unite and take action on the "very serious" situation in Syria, after meetings with China's President Hu Jintao and Foreign Minister Yang Jiechi.
British Foreign Secretary William Hague said that Syria was tipping into chaos and collapse, asserting that a strong UN Security Council stand was needed to push for the creation of a transition government.
"We are aware of reports that the Syrian defence and deputy defence ministers have been killed and a number of others injured by an apparent suicide bombing in Damascus," Hague said in a statement issued in London.
"This incident, which we condemn, confirms the urgent need for a Chapter VII resolution of the UN Security Council on Syria."
However, a UK Foreign and Commonwealth Office (FCO) spokesman told Ahram Online that London insists on a peaceful settlement to the Syrian crisis.
"For the time being, there is no talk within NATO headquarters about military action," a UK mission spokeswoman told Ahram Online.
She added that there was no threat to the national security of any of the NATO members, which is a prerequisite for the organisation to consider military action.
"Any role for NATO in military action in Syria needs a UN Security Council resolution," the spokeswoman confirmed.
French Foreign Minister Laurent Fabius said Wednesday that the suicide bombing confirmed the urgent need for political transition in the country.
"The French government, without knowing the circumstances of this attack, has always condemned terrorism. That said, given the level of violence, this makes it even more necessary and urgent to find a political transition," Fabius told the French Senate.
"We do not yet know the exact circumstances in which this attack took place," Fabius said. "It is an act of extreme importance; this shows the level of violence that has been reached even in Damascus."
German Chancellor Angela Merkel said the suicide attack underlined the "urgent" need for a new UN resolution on Syria.
"This shows that it is urgent that the next UN resolution be passed, on which all states in the international community should work so that the abuse of human rights stops and the political process can move forward," she said.
"You see that such a solution has not been possible. That is why I urge all those on the UN Security Council to agree on a joint resolution."
The UN Security Council had been expected to vote later Wednesday on a Western-backed resolution to consider sanctions if Al-Assad's forces do not withdraw heavy weapons from Syrian cities within ten days.
Britain – with the backing of France, the United States, Germany and Portugal – has proposed a resolution under Chapter 7 of the UN Charter, which threatens non-military sanctions if Al-Assad does not halt the use of heavy weapons within ten days of a resolution being passed.
UN ambassadors from the five countries planned to hold their own talks before announcing whether the vote would go ahead, diplomats said.
However, UN-Arab League envoy Kofi Annan asked the UN Security Council on Wednesday afternoon to delay the vote, British diplomats said.
"Joint Special Envoy Annan has asked to delay today's draft Syria resolution vote. With fellow co-sponsors we're considering that request," a British spokesman said in a statement posted on Twitter.
"Annan feels it is still possible to get a compromise with Russia on the resolution," said a diplomat from another UN Security Council nation, confirming the move.
Russia, for its part, continued to fiercely oppose the threat of sanctions.
Russian President Vladimir Putin and his US counterpart Barack Obama were unable to solve their differences on Syria in a phone conversation Wednesday after the Damascus bombing, the Kremlin said.
"Differences in approaches remain that concern practical steps in achieving a settlement," Russian news agencies quoted Kremlin spokesman Dmitry Peskov as saying.