The Britain-based Syrian Observatory for Human Rights said government forces carried out at least 12 airstrikes and dropped at least nine barrel bombs on rebel-held parts of Daraa as intense clashes with insurgents, including members of the al-Qaida-linked Levant Liberation Committee, continued in the city's Manshiyeh neighborhood.
The monitoring group added that at least two rockets were launched by government forces in the area. The activist-run Step News Agency and Qasioun News Agency also reported clashes and shelling in the southern city.
Russia, Iran and Turkey agreed to establish the zones in Syria, signing on to a Russian plan under which President Bashar Assad's air force would halt flights over designated areas across the war-torn country. Russia says maps delineating the zones should be ready by June 4.
Daraa province, where protests against Assad's rule first began in March 2011, is one of four "de-escalation zones" announced earlier this month during cease-fire talks in Astana, Kazakhstan. Daraa is contested between Syrian rebels and the government, but militant groups also hold pockets in the province, near the border with Jordan.
This week's clashes are among the worst since the so-called de-escalation agreement. Intense clashes in Daraa began on Monday between government forces and insurgents with both sides shelling parts of the southern city.
Russia's defense minister, meanwhile, said the deal to set up the zones is "the main document to end Syria's civil war." Sergei Shoigu said Moscow has been discussing safe zones in Syria with several nations, including the United States, Israel and Jordan.
Shoigu said Russia has been working with Turkey and Iran to prepare for the deployment of a monitoring force to patrol safety zones once all the specifics are set at next month's meeting in Astana. Also Wednesday, activists reported that a suspected coalition airstrike in rural Raqqa province late Tuesday has killed at least 16 civilians, including five children from the same family. The Observatory said the late night airstrike hit Barouda, a village 15 kilometers (9 miles) west of Raqqa city, the de-facto capital of the Islamic State militants. The Observatory and the activist-operated Raqqa is Being Slaughtered Silently group said the 16 were mostly from the same family and have been displaced from another area south of Raqqa controlled by IS.
In response to an Associated Press e-mailed query, the U.S.-led international coalition leading the campaign against IS in Syria's northeast said it would forward the allegation to its assessment team "to be looked at more closely."
"Our goal has always been for zero civilian casualties, but the Coalition will not abandon our commitment to our partners because of ISIS's brutal tactics terrorizing civilians, using human shields, and fighting from protected sites such as schools, hospitals and religious sites," it said.
The campaign to chase IS out of Raqqa, which began late last year, has picked up steam recently, as the U.S. administration declared it will provide more weapons to its main partner on the ground, the Kurdish-led Syrian Democratic Forces.
On Wednesday, the SDF said it seized a village five kilometers (three miles) east of Raqqa city following three days of clashes with IS militants. The SDF has closed in on the city from the east, south east, and north. The force also seized from IS the strategic Tabqa town and its dam to the west of Raqqa earlier this month.