Israel said the Damascus strike was a “clear message” to the government not to harm the Druze minority, following recent sectarian clashes.
The strikes came after Druze clerics and armed factions reaffirmed their loyalty to Damascus. They urged the new authorities to appoint local officials to government posts in Sweida province, heartland of the Druze religious group.
An apparent drone strike killed four Druze fighters at a farm in Sweida, the Observatory said. It was unclear who staged the strike, but Syria's official SANA news agency said it was an Israeli attack.
The observatory reported more than 20 night time Israeli strikes overall on the regions, calling them the heaviest since the start of the year.
The early morning blast in the presidential palace area of Damascus was heard across the city.
In a joint statement, Israeli Prime Minister Benjamin Netanyahu and Defence Minister Israel Katz called it a “clear message” to Syria's new rulers.
Syria's presidency called the strike “a dangerous escalation against state institutions”, and accused Israel of destabilising the country.
The UN-mandated Independent Commission of Inquiry on Syria expressed concern at the “deadly clashes with sectarian dimensions”, and said Israeli air strikes increased the risk to civilians.
Syrian officials said the agreement also included the immediate surrender of heavy weapons.
'Outlaw groups'
Israel has attacked hundreds of military sites since Islamist-led forces deposed longtime president Bashar al-Assad in December.
Israel launched strikes near Damascus on Wednesday and threatened more if violence against the Druze continued.
Syria's government said “outlaw groups” were behind the violence, but the Observatory and Druze residents said forces affiliated with the new authorities attacked Jaramana and Sahnaya and clashed with Druze gunmen.
Mohamad Halawa, a security official in Damascus province, said there was a security cordon around Jaramana where residents would be “under the umbrella of the state and the judiciary”.
SANA said security forces were being sent to Sweida to “maintain security”.
Syria's new authorities have roots in the Al-Qaeda jihadist network. They have vowed inclusive rule in the multi-confessional, multi-ethnic country, but must also contend with internal pressures from radical Islamists.
The latest violence follows massacres of Alawites in March, when the Observatory said the security forces and their allies killed more than 1,700 civilians.
The government accused Assad loyalists of sparking the violence, and launched an inquiry.
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